Skip to content
Login Register

#CDK inhibitor

3 public questions tagged with this topic.

Cell Cycle Regulation

The role of p27 in G1 phase is to:

p27Kip1 product of CDKN1B gene exemplifies Cip/Kip family that imposes G1 arrest and integrates nutrient availability with size control. In quiescent and early G1 cells, p27 accumulates due to low proteasomal turnover and binds cyclin E-CDK2 heterodimer, inserting 3_10 helix into ATP-binding pocket, preventing catalysis and blocking Rb phosphorylation, maintaining E2F repression. This prevents premature S-phase entry when growth factors limited. Mitogen signaling induces cyclin D-CDK4/6 complexes that sequester p27 in trimeric assembly without fully inhibiting them, lowering free p27 pool. Sub

Ref: Sherr & Roberts, Genes & Dev 2004, p27 Biology. Morgan, Cell Cycle, Chapter 4, G1 Control.

View Details
Cell Cycle Regulation

The protein p16 (INK4) primarily inhibits:

INK4 family represents dedicated inhibitors of CDK4 and CDK6 distinguishing them from Cip/Kip family that target cyclin E-CDK2 and cyclin A-CDK2. p16INK4a product of CDKN2A locus contains four ankyrin repeats forming elongated structure that binds CDK6 opposite cyclin-binding interface, inducing distortion of ATP-binding pocket and preventing association with cyclin D. Since cyclin D-CDK4/6 is earliest kinase phosphorylating Rb in response to mitogens, its inhibition maintains Rb in hypophosphorylated active repressor state bound to E2F, arresting cell before restriction point. Genetic inactiv

Ref: Sherr & Roberts, Genes & Dev 1999, INK4 Family Biology. Alberts 7th ed., Chapter 20.

View Details
Cell Cycle Regulation

The major function of p21 in the cell cycle is to:

p21WAF1/CIP1 encoded by CDKN1A represents broad-spectrum cyclin-dependent kinase inhibitor linking DNA damage response to cell cycle arrest in G1 and G2. Upon double-strand break detection, ATM kinase phosphorylates Chk2 and p53 at serine 15, blocking MDM2-mediated ubiquitination and stabilizing p53. ATR responds to single-stranded DNA coated with RPA. Accumulated p53 binds response elements in CDKN1A promoter, markedly upregulating p21 protein that contains N-terminal CDK inhibitory domain with Cy1 and Cy2 cyclin-binding motifs. p21 inserts into catalytic cleft of cyclin E-CDK2, cyclin D-CDK4

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 17: p53-p21 DNA Damage Axis.

View Details