Retinoblastoma protein
Encyclopedia
The retinoblastoma protein (abbreviated pRb, RB or RB1) is a tumor suppressor protein
that is dysfunctional in the majority types of cancer
. One highly studied function of pRb is to prevent excessive cell
growth by inhibiting cell cycle
progression until a cell is ready to divide. It is also a recruiter of several chromatin remodeling
enzymes such as methylases and acetylases.
pRb belongs to the pocket protein family
, whose members have a pocket for the functional binding of other proteins. Should an oncogenic protein, such as those produced by cells infected by high-risk types of human papillomavirus
es, bind and inactivate pRb, this can lead to cancer.
. If both allele
s of this gene are mutated early in life, the protein is inactivated and results in development of retinoblastoma
cancer, hence the name Rb. It is not known why an eye cancer results from a mutation in a gene that is important all over the body.
Two forms of retinoblastoma were noticed: a bilateral, familial form and a unilateral, sporadic form. Sufferers of the former were 6 times more likely to develop other types of cancer later in life. This highlighted the fact that mutated Rb could be inherited and lent support to the two-hit hypothesis. This states that only one working allele of a tumour suppressor gene is necessary for its function (the mutated gene is recessive), and so both need to be mutated before the cancer phenotype will appear. In the familial form, a mutated allele is inherited along with a normal allele. In this case, should a cell sustain only one mutation in the other RB gene, all pRb in that cell would be ineffective at inhibiting cell cycle progression, allowing cells to divide uncontrollably and eventually become cancerous. Furthermore, as one allele is already mutated in all other somatic cells, the future incidence of cancers in these individuals is observed with linear
kinetics. The working allele need not undergo a mutation per se, as loss of heterozygosity
(LOH) is frequently observed in such tumours.
However, in the sporadic form, both alleles would need to sustain a mutation before the cell can become cancerous. This explains why sufferers of sporadic retinoblastoma are not at increased risk of cancers later in life, as both alleles are functional in all their other cells. Future cancer incidence in sporadic Rb cases is observed with polynomial
kinetics, not exactly quadratic
as expected because the first mutation must arise through normal mechanisms, and then can be duplicated by LOH to result in a tumour progenitor
.
RB1 orthologs have also been identified in most mammals for which complete genome data are available.
pRB/E2F-family proteins repression transcription.
s of the E2F
family, which are composed of dimers of an E2F protein and a DP protein. The transcription
activating complexes of E2 promoter-binding–protein-dimerization partners (E2F-DP) can push a cell into S phase. As long as E2F-DP is inactivated, the cell remains stalled in the G1 phase. When pRb is bound to E2F, the complex acts as a growth suppressor and prevents progression through the cell cycle. The pRb-E2F/DP complex also attracts a histone deacetylase
(HDAC) protein to the chromatin
, reducing transcription of S phase promoting factors, further suppressing DNA synthesis
.
state, pRb is active and carries out its role as tumor suppressor by inhibiting cell cycle progression. Phosphorylation inactivates pRb. During the M-to-G1 transition, pRb is progressively dephosphorylated by PP1, returning to its growth-suppressive hypophosphorylated state .
When it is time for a cell to enter S phase, complexes of cyclin-dependent kinase
s (CDK) and cyclin
s phosphorylate pRb, inhibiting its activity. The initial phosphorylation is performed by Cyclin D
/CDK4/CDK6 and followed by additional phosphorylation by Cyclin E/CDK2. pRb remains phosphorylated throughout S, G2 and M phases.
Phosphorylation of pRb allows E2F-DP to dissociate from pRb and become active. When E2F is free it activates factors like cyclins (e.g. Cyclin E and A), which push the cell through the cell cycle by activating cyclin-dependent kinases, and a molecule called proliferating cell nuclear antigen, or PCNA
, which speeds DNA replication and repair
by helping to attach polymerase
to DNA.
with:
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that is dysfunctional in the majority types of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. One highly studied function of pRb is to prevent excessive cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
growth by inhibiting cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
progression until a cell is ready to divide. It is also a recruiter of several chromatin remodeling
Chromatin remodeling
Chromatin remodeling is the enzyme-assisted movement of nucleosomes on DNA.This is performed by chromatin remodeling complexes like SWI/SNF , RSC and Imitation SWI complexes ....
enzymes such as methylases and acetylases.
pRb belongs to the pocket protein family
Pocket protein family
Pocket protein family consists of three proteins:* RB – Retinoblastoma protein* p107 – Retinoblastoma-like protein 1* p130 – Retinoblastoma-like protein 2...
, whose members have a pocket for the functional binding of other proteins. Should an oncogenic protein, such as those produced by cells infected by high-risk types of human papillomavirus
Human papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...
es, bind and inactivate pRb, this can lead to cancer.
Name and genetics
In humans, the protein is encoded by the RB1 gene located on 13q14.1-q14.2Chromosome 13 (human)
Chromosome 13 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 13 spans about 114 million base pairs and represents between 3.5 and 4 % of the total DNA in cells....
. If both allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
s of this gene are mutated early in life, the protein is inactivated and results in development of retinoblastoma
Retinoblastoma
Retinoblastoma is a rapidly developing cancer that develops in the cells of retina, the light-detecting tissue of the eye. In the developed world, Rb has one of the best cure rates of all childhood cancers , with more than nine out of every ten sufferers surviving into...
cancer, hence the name Rb. It is not known why an eye cancer results from a mutation in a gene that is important all over the body.
Two forms of retinoblastoma were noticed: a bilateral, familial form and a unilateral, sporadic form. Sufferers of the former were 6 times more likely to develop other types of cancer later in life. This highlighted the fact that mutated Rb could be inherited and lent support to the two-hit hypothesis. This states that only one working allele of a tumour suppressor gene is necessary for its function (the mutated gene is recessive), and so both need to be mutated before the cancer phenotype will appear. In the familial form, a mutated allele is inherited along with a normal allele. In this case, should a cell sustain only one mutation in the other RB gene, all pRb in that cell would be ineffective at inhibiting cell cycle progression, allowing cells to divide uncontrollably and eventually become cancerous. Furthermore, as one allele is already mutated in all other somatic cells, the future incidence of cancers in these individuals is observed with linear
Linear function
In mathematics, the term linear function can refer to either of two different but related concepts:* a first-degree polynomial function of one variable;* a map between two vector spaces that preserves vector addition and scalar multiplication....
kinetics. The working allele need not undergo a mutation per se, as loss of heterozygosity
Loss of heterozygosity
Loss of heterozygosity in a cell is the loss of normal function of one allele of a gene in which the other allele was already inactivated. This term is mostly used in the context of oncogenesis; after an inactivating mutation in one allele of a tumor suppressor gene occurs in the parent's germline...
(LOH) is frequently observed in such tumours.
However, in the sporadic form, both alleles would need to sustain a mutation before the cell can become cancerous. This explains why sufferers of sporadic retinoblastoma are not at increased risk of cancers later in life, as both alleles are functional in all their other cells. Future cancer incidence in sporadic Rb cases is observed with polynomial
Polynomial
In mathematics, a polynomial is an expression of finite length constructed from variables and constants, using only the operations of addition, subtraction, multiplication, and non-negative integer exponents...
kinetics, not exactly quadratic
Quadratic
In mathematics, the term quadratic describes something that pertains to squares, to the operation of squaring, to terms of the second degree, or equations or formulas that involve such terms...
as expected because the first mutation must arise through normal mechanisms, and then can be duplicated by LOH to result in a tumour progenitor
Cancer stem cell
Cancer stem cells are cancer cells that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. CSCs are therefore tumorigenic , perhaps in contrast to other non-tumorigenic cancer cells...
.
RB1 orthologs have also been identified in most mammals for which complete genome data are available.
pRB/E2F-family proteins repression transcription.
Cell cycle suppression
pRb prevents the cell from replicating damaged DNA by preventing its progression along the cell cycle through G1 (first gap phase) into S (synthesis phase). pRb binds and inhibits transcription factorTranscription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
s of the E2F
E2F
E2F is a group of genes that codifies a family of transcription factors in higher eukaryotes. Three of them are activators: E2F1, 2 and E2F3a. Six others act as suppressors: E2F3b, E2F4-8. All of them are involved in the cell cycle regulation and synthesis of DNA in mammalian cells...
family, which are composed of dimers of an E2F protein and a DP protein. The transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
activating complexes of E2 promoter-binding–protein-dimerization partners (E2F-DP) can push a cell into S phase. As long as E2F-DP is inactivated, the cell remains stalled in the G1 phase. When pRb is bound to E2F, the complex acts as a growth suppressor and prevents progression through the cell cycle. The pRb-E2F/DP complex also attracts a histone deacetylase
Histone deacetylase
Histone deacetylases are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. This is important because DNA is wrapped around histones, and DNA expression is regulated by acetylation and de-acetylation. Its action is opposite to that of histone...
(HDAC) protein to the chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
, reducing transcription of S phase promoting factors, further suppressing DNA synthesis
DNA synthesis
DNA synthesis commonly refers to:*DNA replication - DNA biosynthesis *Polymerase chain reaction - enzymatic DNA synthesis *Oligonucleotide synthesis - chemical synthesis of nucleic acids...
.
Detection
Several methods for detecting the RB1 gene mutations have been developed including a method that can detect large deletions that correlate with advanced stage retinoblastoma.Activation and inactivation
In the hypophosphorylatedPhosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
state, pRb is active and carries out its role as tumor suppressor by inhibiting cell cycle progression. Phosphorylation inactivates pRb. During the M-to-G1 transition, pRb is progressively dephosphorylated by PP1, returning to its growth-suppressive hypophosphorylated state .
When it is time for a cell to enter S phase, complexes of cyclin-dependent kinase
Cyclin-dependent kinase
thumb|350px|Schematic of the cell cycle. outer ring: I=[[Interphase]], M=[[Mitosis]]; inner ring: M=Mitosis; G1=[[G1 phase|Gap phase 1]]; S=[[S phase|Synthesis]]; G2=[[G2 phase|Gap phase 2]]...
s (CDK) and cyclin
Cyclin
Cyclins are a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase enzymes.- Function :...
s phosphorylate pRb, inhibiting its activity. The initial phosphorylation is performed by Cyclin D
Cyclin D
Cyclin D is a member of the cyclin protein family that is involved in regulating cell cycle progression. The synthesis of cyclin D is initiated during G1 and drives the G1/S phase transition...
/CDK4/CDK6 and followed by additional phosphorylation by Cyclin E/CDK2. pRb remains phosphorylated throughout S, G2 and M phases.
Phosphorylation of pRb allows E2F-DP to dissociate from pRb and become active. When E2F is free it activates factors like cyclins (e.g. Cyclin E and A), which push the cell through the cell cycle by activating cyclin-dependent kinases, and a molecule called proliferating cell nuclear antigen, or PCNA
PCNA
Proliferating Cell Nuclear Antigen, commonly known as PCNA, is a protein that acts as a processivity factor for DNA polymerase δ in eukaryotic cells. It achieves this processivity by encircling the DNA, thus creating a topological link to the genome...
, which speeds DNA replication and repair
DNA repair
DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...
by helping to attach polymerase
DNA polymerase
A DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....
to DNA.
Interactions
Retinoblastoma protein has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with:
- Abl geneAbl geneV-abl Abelson murine leukemia viral oncogene homolog 1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene located on chromosome 9.- Function :...
, - Androgen receptorAndrogen receptorThe androgen receptor , also known as NR3C4 , is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus...
, - Apoptosis antagonizing transcription factorApoptosis antagonizing transcription factorProtein AATF is a protein that in humans is encoded by the AATF gene.-Interactions:Apoptosis-antagonizing transcription factor has been shown to interact with Sp1 transcription factor, POLR2J, PAWR and Retinoblastoma protein.- External links :...
, - ARID4AARID4AAT rich interactive domain 4A , also known as ARID4A, is a protein which in humans is encoded by the ARID4A gene.- Function :...
, - Aryl hydrocarbon receptorAryl hydrocarbon receptorThe Aryl hydrocarbon receptor is a member of the family of basic-helix-loop-helix transcription factors. AhR is a cytosolic transcription factor that is normally inactive, bound to several co-chaperones...
, - BRCA1BRCA1BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...
, - BRF1BRF1 (gene)Transcription factor IIIB 90 kDa subunit is a protein that in humans is encoded by the BRF1 gene.-Interactions:BRF1 has been shown to interact with Retinoblastoma-like protein 2, Retinoblastoma-like protein 1, TATA binding protein and Retinoblastoma protein.-External links:...
, - C-junC-junc-Jun is the name of a gene and protein that, in combination with c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the c-jun gene. It is activated through double phosphorylation by the...
, - C-RafC-RafRAF proto-oncogene serine/threonine-protein kinase also known as proto-oncogene c-RAF or simply c-Raf is an enzyme that in humans is encoded by the RAF1 gene. The c-Raf protein functions in the MAPK/ERK signal transduction pathway as part of a protein kinase cascade...
, - CDK9CDK9CDK9 or cyclin-dependent kinase 9 is a cyclin-dependent kinase associated with P-TEFb.CDK9 is also known to associate with other proteins such as TRAF2, and be involved in differentiation of skeletal muscle...
, - CUTL1CUTL1Cux1 is a homeodomain protein that in humans is encoded by the CUX1 gene.-Interactions:Cux1 has been shown to interact with CREB binding protein, SATB1 and Retinoblastoma protein....
, - Cyclin A1,
- Cyclin D1Cyclin D1G1/S-specific cyclin-D1 is a protein that in humans is encoded by the CCND1 gene.Immunohistochemical staining of cyclin D1 antibodies is used to diagnose mantle cell lymphoma.-Interactions:...
, - Cyclin T2,
- DNMT1DNMT1DNA -methyltransferase 1 is an enzyme that in humans is encoded by the DNMT1 gene.-Interactions:DNMT1 has been shown to interact with Histone deacetylase 2, DMAP1, PCNA, Retinoblastoma protein, DNMT3A and DNMT3B.-Further reading:...
, - E2F1E2F1Transcription factor E2F1 is a protein that in humans is encoded by the E2F1 gene.-Interactions:E2F1 has been shown to interact with NCOA6, Retinoblastoma-like protein 1, Retinoblastoma protein, GTF2H1, SKP2, PURA, NPDC1, Sp2 transcription factor, Sp1 transcription factor, CUL1, ARID3A, TOPBP1,...
, - E2F2E2F2Transcription factor E2F2 is a protein that in humans is encoded by the E2F2 gene.-Interactions:E2F2 has been shown to interact with BRD2, Retinoblastoma protein and RYBP....
, - E4F1E4F1Transcription factor E4F1 is a protein that in humans is encoded by the E4F1 gene.-Interactions:E4F1 has been shown to interact with P16, Retinoblastoma protein and P53....
, - EID1EID1EP300-interacting inhibitor of differentiation 1 is a protein that in humans is encoded by the EID1 gene.-Interactions:EID1 has been shown to interact with EP300 and Retinoblastoma protein.-Further reading:...
, - ENC1ENC1Ectoderm-neural cortex protein 1 is a protein that in humans is encoded by the ENC1 gene.-Interactions:ENC1 has been shown to interact with Retinoblastoma protein.-Further reading:...
, - FRKFRK (gene)Fyn-related kinase is an enzyme that in humans is encoded by the FRK gene.-Interactions:FRK has been shown to interact with retinoblastoma protein.-Further reading:...
, - HBP1HBP1HMG-box transcription factor 1, also known as HBP1, is a human protein.-Interactions:HBP1 has been shown to interact with SIN3A and Retinoblastoma protein.-Further reading:...
, - HDAC1HDAC1Histone deacetylase 1 is an enzyme that in humans is encoded by the HDAC1 gene.-Interactions:HDAC1 has been shown to interact with RAD9A, DNMT3L, MTA1, FKBP3, CDC20, CDH1, Host cell factor C1, BUB3, Nuclear receptor co-repressor 2, IKZF1, Prohibitin, EVI1, DDX5, DNMT3A, Mothers against...
, - HDAC3HDAC3Histone deacetylase 3 is an enzyme that in humans is encoded by the HDAC3 gene.-Interactions:HDAC3 has been shown to interact with HDAC9, HDAC7A, Retinoblastoma protein, RBBP4, Testicular receptor 2, MAP3K7IP2, Peroxisome proliferator-activated receptor delta, GTF2I, Histone deacetylase 5, RELA,...
, - Histone deacetylase 2Histone deacetylase 2Histone deacetylase 2 is an enzyme that in humans is encoded by the HDAC2 gene.-Interactions:Histone deacetylase 2 has been shown to interact with CHD3, MTA1, FKBP3, CHD4, RCOR1, Retinoblastoma protein, CDC20, RBBP4, CDH1, EED, GTF2I, Host cell factor C1, PHF21A, BUB3, MXD1, HDAC10, RELA, Sp3...
, - JARID1AJARID1ALysine-specific demethylase 5A is an enzyme that in humans is encoded by the KDM5A gene.The Drosophila homolog, LID, was found to be an H3K4 histone demethylase that binds to c-Myc. It was recently renamed to Lysine Demethylase 5A ....
, - LIN9LIN9Lin-9 homolog is a protein that in humans is encoded by the LIN9 gene.-Interactions:LIN9 has been shown to interact with Retinoblastoma protein.-Further reading:...
, - MCM7MCM7DNA replication licensing factor MCM7 is a protein that in humans is encoded by the MCM7 gene.-Interactions:MCM7 has been shown to interact with Replication protein A1, ORC3L, Retinoblastoma protein, MCM5, MCM6, ORC1L, ORC2L, ORC5L, MCM4, MCM3, CDC6, MNAT1, DBF4, MCM2, UBE3A, CDC45-related protein...
, - MORF4L1MORF4L1Mortality factor 4-like protein 1 is a protein that in humans is encoded by the MORF4L1 gene.-Interactions:MORF4L1 has been shown to interact with MYST1, Retinoblastoma protein and MRFAP1.-Further reading:...
, - MRFAP1MRFAP1MORF4 family-associated protein 1 is a protein that in humans is encoded by the MRFAP1 gene.-Interactions:MRFAP1 has been shown to interact with MORF4L1 and Retinoblastoma protein.-Further reading:...
, - MyoDMyoDMyoD is a protein with a key role in regulating muscle differentiation. MyoD belongs to a family of proteins known as myogenic regulatory factors . These bHLH transcription factors act sequentially in myogenic differentiation. MRF family members include MyoD, Myf5, myogenin, and MRF4 .MyoD is one...
, - NCOA6NCOA6Nuclear receptor coactivator 6 is a protein that in humans is encoded by the NCOA6 gene.-Interactions:NCOA6 has been shown to interact with Ku70, RBBP5, E2F1, Retinoblastoma protein, CREB-binding protein, Activating transcription factor 2, HSF1, HBXIP, TGS1, TUBB, TUBA4A, Thyroid hormone receptor...
, - PA2G4PA2G4Proliferation-associated protein 2G4 is a protein that in humans is encoded by the PA2G4 gene.-Interactions:PA2G4 has been shown to interact with ERBB3, Retinoblastoma protein and Androgen receptor.-Further reading:...
, - Peroxisome proliferator-activated receptor gammaPeroxisome proliferator-activated receptor gammaPeroxisome proliferator-activated receptor gamma , also known as the glitazone receptor, or NR1C3 is a type II nuclear receptor that in humans is encoded by the PPARG gene.Two isoforms of PPARG are detected in the human and in the mouse: PPAR-γ1 and...
, - PIK3R3PIK3R3Phosphatidylinositol 3-kinase regulatory subunit gamma is an enzyme that in humans is encoded by the PIK3R3 gene.-Interactions:PIK3R3 has been shown to interact with Insulin-like growth factor 1 receptor, IRS1 and Retinoblastoma protein....
, - Plasminogen activator inhibitor-2Plasminogen activator inhibitor-2Plasminogen activator inhibitor-2 is a coagulation factor that inactivates tPA and urokinase. It is present in most cells, especially monocytes/macrophages...
, - Polymerase (DNA directed), alpha 1,
- PRDM2PRDM2PR domain zinc finger protein 2 is a protein that in humans is encoded by the PRDM2 gene.-Interactions:PRDM2 has been shown to interact with Estrogen receptor alpha and Retinoblastoma protein.- External links :...
, - PRKRAPRKRAProtein kinase, interferon-inducible double stranded RNA dependent activator, also known as interferon-inducible double stranded RNA-dependent protein kinase activator A or Protein ACTivator of the interferon-induced protein kinase is a protein that in humans is encoded by the PRKRA gene...
, - ProhibitinProhibitinProhibitin, also known as PHB, is a protein that in humans is encoded by the PHB gene.The Phb gene has also been described in animals, fungi, plants, and unicellular eukaryotes. Prohibitins are divided in two classes, termed Type-I and Type-II prohibitins, based on their similarity to yeast PHB1...
, - Promyelocytic leukemia proteinPromyelocytic leukemia proteinProbable transcription factor PML is a tumor suppressor protein that in humans is encoded by the PML gene.-Interactions:Promyelocytic leukemia protein has been shown to interact with Retinoic acid receptor alpha, HDAC1, Nerve Growth factor IB, SKI protein, Zinc finger and BTB domain-containing...
, - RBBP4RBBP4Histone-binding protein RBBP4 is a protein that in humans is encoded by the RBBP4 gene.-Interactions:RBBP4 has been shown to interact with HDAC1, Histone deacetylase 2, SIN3A, Retinoblastoma protein, SAP30, CREB-binding protein, GATAD2B, BRCA1, MTA2 and HDAC3.-Further reading:...
, - RBBP7RBBP7Histone-binding protein RBBP7 is a protein that in humans is encoded by the RBBP7 gene.-Interactions:RBBP7 has been shown to interact with HDAC1, MTA2, SIN3A, Retinoblastoma protein, SAP30, GATAD2B and BRCA1.-Further reading:...
, - RBBP8RBBP8Retinoblastoma-binding protein 8 is a protein that in humans is encoded by the RBBP8 gene.-Interactions:RBBP8 has been shown to interact with LMO4, Retinoblastoma-like protein 2, Retinoblastoma-like protein 1, Ataxia telangiectasia mutated, Retinoblastoma protein, CTBP1, SIAH1 and BRCA1.-Further...
, - RBBP9RBBP9Putative hydrolase RBBP9 is an enzyme that in humans is encoded by the RBBP9 gene.-Interactions:RBBP9 has been shown to interact with Retinoblastoma protein.-Further reading:...
, - SNAPC1SNAPC1snRNA-activating protein complex subunit 1 is a protein that in humans is encoded by the SNAPC1 gene.-Interactions:SNAPC1 has been shown to interact with SNAPC4, SNAPC3 and Retinoblastoma protein.-Further reading:...
, - SKP2SKP2S-phase kinase-associated protein 2 is an enzyme that in humans is encoded by the SKP2 gene.- Function :This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box domain...
, - SNAPC3SNAPC3snRNA-activating protein complex subunit 3 is a protein that in humans is encoded by the SNAPC3 gene.-Interactions:SNAPC3 has been shown to interact with SNAPC1 and Retinoblastoma protein.-Further reading:...
, - SNW1SNW1SNW domain-containing protein 1 is a protein that in humans is encoded by the SNW1 gene.-Interactions:SNW1 has been shown to interact with Histone deacetylase 2, SKI protein, Retinoblastoma protein, PABPN1, CIR, RBPJ, Nuclear receptor coactivator 1, Nuclear receptor co-repressor 2, Calcitriol...
, - SUV39H1SUV39H1Histone-lysine N-methyltransferase SUV39H1 is an enzyme that in humans is encoded by the SUV39H1 gene.-Interactions:SUV39H1 has been shown to interact with HDAC9, HDAC1, Histone deacetylase 2, Retinoblastoma protein, CBX5, HDAC3, DNMT3A, MBD1, RUNX1, SBF1 and CBX1.-Further reading:...
, - TAF1TAF1Transcription initiation factor TFIID subunit 1, also known as transcription initiation factor TFIID 250 kDa subunit or TBP-associated factor 250 kDa , is a protein that in humans is encoded by the TAF1 gene.-Function:...
, - THOC1THOC1THO complex subunit 1 is a protein that in humans is encoded by the THOC1 gene.-Interactions:THOC1 has been shown to interact with Retinoblastoma protein.-Further reading:...
, - TRAP1TRAP1Heat shock protein 75 kDa, mitochondrial is a protein that in humans is encoded by the TRAP1 gene.-Interactions:TRAP1 has been shown to interact with EXT2, EXT1 and Retinoblastoma protein.-Further reading:...
, - TRIP11TRIP11Thyroid receptor-interacting protein 11 is a protein that in humans is encoded by the TRIP11 gene.-Interactions:TRIP11 has been shown to interact with Retinoblastoma protein and Thyroid hormone receptor alpha.-Further reading:...
, - UBTFUBTFNucleolar transcription factor 1 is a protein that in humans is encoded by the UBTF gene.-Interactions:UBTF has been shown to interact with Casein kinase 2, alpha 1, TAF1C, Retinoblastoma protein and TAF1.-Further reading:...
, and - USP4USP4Ubiquitin carboxyl-terminal hydrolase 4 is an enzyme that in humans is encoded by the USP4 gene. This protein is a member of cysteine peptidase family C19.-Interactions:USP4 has been shown to interact with Retinoblastoma protein.-Further reading:...
.
See also
- p53P53p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
- involved in the DNA repair support function of pRb - Transcription coregulatorTranscription coregulatorIn molecular biology and genetics, transcription coregulators are proteins that interact with transcription factors to either activate or repress the transcription of specific genes. Transcription coregulators that activate gene transcription are referred to as coactivators while those that...
- RetinoblastomaRetinoblastomaRetinoblastoma is a rapidly developing cancer that develops in the cells of retina, the light-detecting tissue of the eye. In the developed world, Rb has one of the best cure rates of all childhood cancers , with more than nine out of every ten sufferers surviving into...
Further reading
External links
- GeneReviews/NIH/NCBI/UW entry on Retinoblastoma
- Retinoblastoma Genetics
- Drosophila Retinoblastoma-family protein - The Interactive Fly
- Drosophila Retinoblastoma-family protein 2 - The Interactive Fly
- There is a diagram of the pRb-E2F interactions here.
