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

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

Stable Identifier

R-HSA-3788705

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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

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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
22178396	DNA damage signaling triggers degradation of histone methyltransferases through APC/C(Cdh1) in senescent cells Peters, G, Yoshimoto, S, Shinkai, Y, Imai, Y, Tachibana, M, Takahashi, A, Saya, H, Takeuchi, T, Hori, S, Hara, E, Kuninaka, S, Yamakoshi, K, Ohtani, N, Anderton, E	Mol. Cell	2012
10548110	Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the anaphase-promoting complex Lukas, J, Lindeneg, C, Peters, JM, Sorensen, CS, Kramer, E, Lukas, C, Santoni-Rugiu, E	Nature	1999