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#p27

2 public questions tagged with this topic.

Cell Cycle Regulation

Which molecule directly targets p27 for ubiquitin-mediated degradation?

Abundance of p27 is controlled post-translationally rather than transcriptionally, illustrating CDK-regulated proteolysis that sharpens G1/S transition. Late in G1, cyclin E-CDK2 phosphorylates p27 intrinsically disordered C-terminus at threonine 187. This phosphate forms high-affinity interaction with WD40 domain of Skp2, F-box protein assembled into SCF-Skp2 E3 ligase with Skp1 adaptor, Cullin1 scaffold, Rbx1 RING finger recruiting Ubc3 E2 enzyme, plus Cks1 cofactor that bridges CDK and F-box. SCF catalyzes formation of K48-linked polyubiquitin chains on p27 lysines, marking it for rapid deg

Ref: Carrano et al., Nature Cell Biology 1999, SCF-Skp2 Targets p27. Alberts 7th ed., Chapter 3.

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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.

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