CDKN1B
Encyclopedia
Cyclin-dependent kinase inhibitor 1B is an enzyme
that in humans is encoded by the CDKN1B gene
. It encodes a protein
which belongs to the Cip/Kip family of cyclin dependent kinase (Cdk) inhibitor proteins. The encoded protein binds to and prevents the activation of cyclin E
-CDK2
or cyclin D
-CDK4
complexes, and thus controls the cell cycle
progression at G1. It is often referred to as a cell cycle
inhibitor protein because its major function is to stop or slow down the cell division cycle.
similar to other members of the "Cip/Kip" family which include the p21
Cip1/Waf1 and p57Kip2 genes. In addition to this structural similarity the "Cip/Kip" proteins share the functional characteristic of being able to bind several different classes of Cyclin and Cdk molecules. For example, p27Kip1 binds to cyclin D
either alone, or when complexed to its catalytic subunit CDK4
. In doing so p27Kip1 inhibits the catalytic activity of Cdk4, which means that it prevents Cdk4 from adding phosphate
residues to its principal substrate
, the retinoblastoma
(pRb
) protein. Increased levels of the p27Kip1 protein typically cause cells to arrest in the G1 phase
of the cell cycle. Likewise, p27Kip1 is able to bind other Cdk proteins when complexed to cyclin subunits such as Cyclin E
/Cdk2 and Cyclin A
/Cdk2.
(IL-2) causes p27Kip1 levels to drop in T-lymphocytes. A mutation of this gene may lead to loss of control over the cell cycle leading to uncontrolled cellular proliferation.
Loss of p27 expression has been observed in metastatic canine mammary carcinomas. Decreased TGF-beta signalling has been suggested to cause loss of p27 expression in this tumor type.
A structured cis-regulatory element
has been found in the 5' UTR of the P27 mRNA where it is thought to regulate translation relative to cell cycle
progression.
with SPDYA
, XPO1
, Cyclin-dependent kinase 2
, SKP2
, Cyclin-dependent kinase 4
, Grb2
, AKT1
, Cyclin D3, Cyclin E1
, NUP50
and CKS1B
.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that in humans is encoded by the CDKN1B gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. It encodes a protein
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...
which belongs to the Cip/Kip family of cyclin dependent kinase (Cdk) inhibitor proteins. The encoded protein binds to and prevents the activation of cyclin E
Cyclin E
Cyclin E is a member of the cyclin family.Cyclin E binds to G1 phase Cdk2, which is required for the transition from G1 to S phase. The Cyclin E/CDK2 complex phosphorylates p27Kip1 , tagging it for degradation, thus promoting expression of Cyclin A, allowing progression to S phase....
-CDK2
Cyclin-dependent kinase 2
Cyclin-dependent kinase 2 also known as cell division protein kinase 2 is an enzyme that in humans is encoded by the CDK2 gene.-Function:...
or 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
Cyclin-dependent kinase 4
Cyclin-dependent kinase 4 is part of the cyclin-dependent kinase family.It is regulated by Cyclin D.-Interactions:Cyclin-dependent kinase 4 has been shown to interact with SERTAD1, CDC37, CEBPA, PCNA, Cyclin D3, Cyclin D1, CDKN2C, MyoD, P16, CDKN2B, Drebrin-like and CDKN1B.-External links:...
complexes, and thus controls the 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 at G1. It is often referred to as a 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...
inhibitor protein because its major function is to stop or slow down the cell division cycle.
Biochemical function
The p27Kip1 gene has a DNA sequenceDNA sequence
The sequence or primary structure of a nucleic acid is the composition of atoms that make up the nucleic acid and the chemical bonds that bond those atoms. Because nucleic acids, such as DNA and RNA, are unbranched polymers, this specification is equivalent to specifying the sequence of...
similar to other members of the "Cip/Kip" family which include the p21
P21
p21 / WAF1 also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1 is a protein that in humans is encoded by the CDKN1A gene located on chromosome 6 .- Function :...
Cip1/Waf1 and p57Kip2 genes. In addition to this structural similarity the "Cip/Kip" proteins share the functional characteristic of being able to bind several different classes of Cyclin and Cdk molecules. For example, p27Kip1 binds to 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...
either alone, or when complexed to its catalytic subunit CDK4
Cyclin-dependent kinase 4
Cyclin-dependent kinase 4 is part of the cyclin-dependent kinase family.It is regulated by Cyclin D.-Interactions:Cyclin-dependent kinase 4 has been shown to interact with SERTAD1, CDC37, CEBPA, PCNA, Cyclin D3, Cyclin D1, CDKN2C, MyoD, P16, CDKN2B, Drebrin-like and CDKN1B.-External links:...
. In doing so p27Kip1 inhibits the catalytic activity of Cdk4, which means that it prevents Cdk4 from adding phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
residues to its principal substrate
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
, the 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...
(pRb
PRB
PRB may refer to:* PRB , the Australian Automotive Manufacturer* PRB * The unofficial ISO 4217 code for the Transnistrian rublePRB is short for:* Powder River Basin, a major coal producing geologic basin in the USA...
) protein. Increased levels of the p27Kip1 protein typically cause cells to arrest in the G1 phase
G1 phase
The G1 phase is a period in the cell cycle during interphase, before the S phase. For many cells, this phase is the major period of cell growth during its lifespan. During this stage new organelles are being synthesized, so the cell requires both structural proteins and enzymes, resulting in great...
of the cell cycle. Likewise, p27Kip1 is able to bind other Cdk proteins when complexed to cyclin subunits such as Cyclin E
Cyclin E
Cyclin E is a member of the cyclin family.Cyclin E binds to G1 phase Cdk2, which is required for the transition from G1 to S phase. The Cyclin E/CDK2 complex phosphorylates p27Kip1 , tagging it for degradation, thus promoting expression of Cyclin A, allowing progression to S phase....
/Cdk2 and Cyclin A
Cyclin A
Cyclin A is a member of the cyclin family.Cyclin A binds to S phase Cdk2 and is required for the cell to progress through the S phase. Cyclin A/ Cdk2 is inhibited by the complex p21CIP.-External links:*...
/Cdk2.
Regulation
In general, extracellular growth factors which prevent cell growth cause an increase in p27Kip1 levels inside a cell. For example, levels of p27Kip1 increase when Transforming Growth Factor β (TGF β) is present outside of epithelial cells causing a growth arrest. In contrast interleukin 2Interleukin 2
Interleukin-2 is an interleukin, a type of cytokine immune system signaling molecule, which is a leukocytotrophic hormone that is instrumental in the body's natural response to microbial infection and in discriminating between foreign and self...
(IL-2) causes p27Kip1 levels to drop in T-lymphocytes. A mutation of this gene may lead to loss of control over the cell cycle leading to uncontrolled cellular proliferation.
Loss of p27 expression has been observed in metastatic canine mammary carcinomas. Decreased TGF-beta signalling has been suggested to cause loss of p27 expression in this tumor type.
A structured cis-regulatory element
P27 cis-regulatory element
The p27 cis-regulatory element is a structured G/C rich RNA element which is involved in controlling cell cycle regulated translation of the p27kip protein in human cells....
has been found in the 5' UTR of the P27 mRNA where it is thought to regulate translation relative to 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.
Interactions
CDKN1B 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 SPDYA
SPDYA
Speedy protein A is a protein that in humans is encoded by the SPDYA gene.-Further reading:...
, XPO1
XPO1
Exportin-1 is a protein that in humans is encoded by the XPO1 gene.-Interactions:XPO1 has been shown to interact with NMD3, CIITA, RANBP3, Nucleoporin 62, Ran, RANBP1, APC, SMARCB1 and CDKN1B.-Further reading:...
, Cyclin-dependent kinase 2
Cyclin-dependent kinase 2
Cyclin-dependent kinase 2 also known as cell division protein kinase 2 is an enzyme that in humans is encoded by the CDK2 gene.-Function:...
, SKP2
SKP2
S-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...
, Cyclin-dependent kinase 4
Cyclin-dependent kinase 4
Cyclin-dependent kinase 4 is part of the cyclin-dependent kinase family.It is regulated by Cyclin D.-Interactions:Cyclin-dependent kinase 4 has been shown to interact with SERTAD1, CDC37, CEBPA, PCNA, Cyclin D3, Cyclin D1, CDKN2C, MyoD, P16, CDKN2B, Drebrin-like and CDKN1B.-External links:...
, Grb2
Grb2
Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene....
, AKT1
AKT1
RAC-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT1 gene. Multiple alternatively spliced transcript variants have been found for this gene.- Function :...
, Cyclin D3, Cyclin E1
Cyclin E1
G1/S-specific cyclin-E1 is a protein that in humans is encoded by the CCNE1 gene.-Interactions:Cyclin E1 has been shown to interact with Retinoblastoma-like protein 2, Cdk1, CDC25A, Cyclin-dependent kinase 2, SMARCA4, CDKN1B, HERC5, CUL3 and P21....
, NUP50
NUP50
Nucleoporin 50 kDa is a protein that in humans is encoded by the NUP50 gene.-Interactions:NUP50 has been shown to interact with KPNB1 and CDKN1B.-Further reading:...
and CKS1B
CKS1B
Cyclin-dependent kinases regulatory subunit 1 is a protein that in humans is encoded by the CKS1B gene.- Function :The CKS1B protein binds to the catalytic subunit of the cyclin-dependent kinases and is essential for their biological function...
.