CDKN1B

CDKN1B is a cyclin-dependent kinase inhibitor, which shares a limited similarity with CDK inhibitor CDKN1A/p21. 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. The degradation of this protein, which is triggered by its CDK dependent phosphorylation and subsequent ubiquitination by SCF complexes, is required for the cellular transition from quiescence to the proliferative state. Mutations in this gene are associated with multiple endocrine neoplasia type IV (MEN4).

Cyclin Dependent Kinase Inhibitor 1B

Important regulator of cell cycle progression. Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA (PubMed:28666995).
Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry.

Autophagic cell death Source: BHF-UCL
Cell cycle arrest Source: HGNC-UCL
Cellular response to lithium ion Source: MGI
Cytokine-mediated signaling pathway Source: Reactome
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: Reactome
G1/S transition of mitotic cell cycle Source: BHF-UCL
Heart development Source: BHF-UCL
Mitotic cell cycle arrest Source: UniProtKB
Negative regulation of cardiac muscle tissue regeneration Source: BHF-UCL
Negative regulation of cell cycle Source: UniProtKB
Negative regulation of cell growth Source: BHF-UCL
Negative regulation of cell population proliferation Source: UniProtKB
Negative regulation of cyclin-dependent protein kinase activity Source: CAFA
Negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
Negative regulation of kinase activity Source: UniProtKB
Negative regulation of mitotic cell cycle Source: UniProtKB
Negative regulation of phosphorylation Source: BHF-UCL
Negative regulation of transcription, DNA-templated Source: UniProtKB
Negative regulation of vascular associated smooth muscle cell proliferation Source: BHF-UCL
Positive regulation of cell cycle Source: Reactome
Positive regulation of cell death Source: UniProtKB
Positive regulation of protein catabolic process Source: MGI
Regulation of cell cycle G1/S phase transition Source: GO_Central
Regulation of cyclin-dependent protein serine/threonine kinase activity Source: GO_Central

Endosome; Nucleus; Cytoplasm. Nuclear and cytoplasmic in quiescent cells. AKT- or RSK-mediated phosphorylation on Thr-198, binds 14-3-3, translocates to the cytoplasm and promotes cell cycle progression. Mitogen-activated UHMK1 phosphorylation on Ser-10 also results in translocation to the cytoplasm and cell cycle progression. Phosphorylation on Ser-10 facilitates nuclear export. Translocates to the nucleus on phosphorylation of Tyr-88 and Tyr-89. Colocalizes at the endosome with SNX6; this leads to lysosomal degradation (By similarity).

Multiple endocrine neoplasia 4 (MEN4): Multiple endocrine neoplasia (MEN) syndromes are inherited cancer syndromes of the thyroid. MEN4 is a MEN-like syndrome with a phenotypic overlap of both MEN1 and MEN2.

Phosphorylated; phosphorylation occurs on serine, threonine and tyrosine residues. Phosphorylation on Ser-10 is the major site of phosphorylation in resting cells, takes place at the G0-G1 phase and leads to protein stability. Phosphorylation on other sites is greatly enhanced by mitogens, growth factors, cMYC and in certain cancer cell lines. The phosphorylated form found in the cytoplasm is inactivate. Phosphorylation on Thr-198 is required for interaction with 14-3-3 proteins. Phosphorylation on Thr-187, by CDK1 and CDK2 leads to protein ubiquitination and proteasomal degradation. Tyrosine phosphorylation promotes this process. Phosphorylation by PKB/AKT1 can be suppressed by LY294002, an inhibitor of the catalytic subunit of PI3K. Phosphorylation on Tyr-88 and Tyr-89 has no effect on binding CDK2, but is required for binding CDK4. Dephosphorylated on tyrosine residues by G-CSF.
Ubiquitinated; in the cytoplasm by the KPC complex (composed of RNF123/KPC1 and UBAC1/KPC2) and, in the nucleus, by SCF(SKP2). The latter requires prior phosphorylation on Thr-187. Ubiquitinated; by a TRIM21-containing SCF(SKP2)-like complex; leads to its degradation.
Subject to degradation in the lysosome. Interaction with SNX6 promotes lysosomal degradation (By similarity).