CDKN1A (p21) prevents phosphorylation of Cdh1 by Cyclin A:Cdk2

Stable Identifier
R-HSA-3788705
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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At the G1/S transition, the Cdh1 (FZR1) subunit of the APC/C:Cdh1 complex is phosphorylated by Cyclin A:Cdk2 (CCNA:CDK2) and dissociates from APC/C. This inactivates APC/C and permits the accumulation of cell cycle proteins required for DNA synthesis and entry into mitosis (Lukas et al. 1999). Activation of the ATM kinase by DNA damage in the form of double strand breaks results in TP53-mediated induction of CDKN1A (p21) expression. CDKN1A binds CCNA:CDK2 complex and prevents it from phosphorylating Cdh1 (Takahashi et al. 2012).

Literature References
PubMed ID Title Journal Year
10548110 Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the anaphase-promoting complex

Lukas, C, Sorensen, CS, Kramer, E, Santoni-Rugiu, E, Lindeneg, C, Peters, JM, Lukas, J

Nature 1999
22178396 DNA damage signaling triggers degradation of histone methyltransferases through APC/C(Cdh1) in senescent cells

Takahashi, A, Imai, Y, Yamakoshi, K, Kuninaka, S, Ohtani, N, Yoshimoto, S, Hori, S, Tachibana, M, Anderton, E, Takeuchi, T, Shinkai, Y, Peters, G, Saya, H, Hara, E

Mol. Cell 2012
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
cyclin-dependent protein serine/threonine kinase activity of Cyclin A:phospho-Cdk(Thr 160):Cdh1:phosho-APC/C complex [nucleoplasm]
Physical Entity
Activity
This event is regulated
Orthologous Events
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Created