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#cyclin

3 public questions tagged with this topic.

Which cyclin accumulates in S phase to promote DNA replication?

Orderly appearance and destruction of cyclins dictates CDK activation windows. Mitogenic stimulation through receptor tyrosine kinases activates Ras-MAPK cascade leading to transcription factor AP-1, Myc, and beta-catenin mediated induction of cyclin D1, D2, D3 genes. Cyclin D proteins accumulate throughout G1, assembling with CDK4 and CDK6 kinases whose activity requires mitogen-dependent stabilization and CAK phosphorylation. Cyclin D-CDK4/6 complexes phosphorylate retinoblastoma proteins at early sites, initiating limited E2F release and transcription of cyclin E. Cyclin E-CDK2 then complet

Ref: Bertoli et al., Nature Reviews Mol Cell Biol 2013, Cyclin Control. Alberts 7th ed., Chapter 17.

Which cyclin accumulates in S phase and promotes DNA replication?

Cyclin abundance oscillates generating waves of CDK activity. Cyclin D induced by mitogens drives early G1 progression, Cyclin E peaks at G1/S boundary initiating replication, then declines rapidly through SCF-Fbw7 mediated degradation after autophosphorylation. Cyclin A accumulates as cells enter and progress through S phase, reaching maximum in G2. Binding partners shift: in S phase, Cyclin A preferentially complexes with CDK2 phosphorylating components for continued DNA synthesis, E2F-dependent transcription termination, centrosome duplication and prevention of origin relicensing such as Cd

Ref: Murray, Cyclins and Cell Cycle Regulation, Cell Cycle Textbook; Alberts et al., Molecular Biology of the Cell, Chapter 17, S-Phase Cyclins.

What is the function of the SCF complex?

Ordered progression through interphase depends on timely degradation of regulatory proteins via ubiquitination. The SCF complex, meaning Skp1-Cullin-F-box, is a modular cullin-RING E3 ligase active from late G1 to early M. Core components include scaffold Cullin1, adaptor Skp1, RING finger Rbx1 and interchangeable F-box protein conferring substrate specificity. Canonical function involves CDK inhibitor p27 Kip1. When Cyclin E-CDK2 phosphorylates p27 at Thr187, phosphodegron is recognized by F-box protein Skp2 together with accessory Cks1, leading to Lys48-linked polyubiquitination and proteaso

Ref: Cardozo & Pagano, SCF Ubiquitin Ligases and Cell Cycle Control, Nat Rev Mol Cell Biol 2004; NCBI, SCF Functions.