CDKN1B Human

Cyclin-Dependent Kinase Inhibitor 1B (CDKN1B), also known as p27^Kip1, is a crucial protein in the regulation of the cell cycle. It is encoded by the CDKN1B gene in humans and belongs to the Cip/Kip family of cyclin-dependent kinase (CDK) inhibitor proteins . This protein plays a significant role in controlling cell cycle progression at the G1 phase by inhibiting cyclin-CDK complexes .

CDKN1B is a potent inhibitor of cyclin E-CDK2 and cyclin D-CDK4 complexes . By binding to these complexes, CDKN1B prevents their activation, thereby halting the cell cycle progression . This inhibition is crucial for maintaining proper cell cycle control and preventing uncontrolled cell proliferation, which can lead to cancer .

The protein structure of CDKN1B includes several domains that facilitate its binding to cyclin-CDK complexes. These domains are conserved among the Cip/Kip family members, which include p21^Cip1/Waf1 and p57^Kip2 .

The expression and activity of CDKN1B are tightly regulated by various extracellular signals and intracellular mechanisms . Growth factors that promote cell division typically reduce the transcription and translation of CDKN1B . Additionally, the synthesis of CDK4/6-cyclin D complexes can sequester CDKN1B, preventing it from inhibiting CDK2-cyclin E complexes .

Phosphorylation of CDKN1B by active CDK2-cyclin E complexes tags it for ubiquitination and subsequent degradation . This degradation is necessary for the transition of cells from the quiescent state to the proliferative state .

Mutations or alterations in the expression of CDKN1B can lead to various pathological conditions, including cancer . Loss of CDKN1B expression has been observed in several types of cancers, such as metastatic canine mammary carcinomas . Decreased signaling of transforming growth factor-beta (TGF-β) has been suggested to cause the loss of CDKN1B expression in these tumors .

Furthermore, mutations in the CDKN1B gene are associated with multiple endocrine neoplasia type IV (MEN4) and primary hyperparathyroidism . These conditions highlight the importance of CDKN1B in maintaining normal cell cycle regulation and preventing tumorigenesis.

Recombinant CDKN1B is produced using various expression systems, such as E. coli, to study its function and potential therapeutic applications . The recombinant protein typically includes tags, such as His-tags, to facilitate its purification and detection . These recombinant proteins are used in research to understand the molecular mechanisms of CDKN1B and to develop potential cancer therapies targeting CDK-cyclin complexes .