Reactome | Inactivation of Cyclin E:Cdk2 complexes by p27/p21

Inactivation of Cyclin E:Cdk2 complexes by p27/p21

Stable Identifier

R-HSA-69562

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

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Cell Cycle (Homo sapiens)

- Cell Cycle Checkpoints (Homo sapiens)
  - G1/S DNA Damage Checkpoints (Homo sapiens)
    - p53-Dependent G1/S DNA damage checkpoint (Homo sapiens)
      - p53-Dependent G1 DNA Damage Response (Homo sapiens)
        
        Inactivation of Cyclin E:Cdk2 complexes by p27/p21 (Homo sapiens)
- Cell Cycle, Mitotic (Homo sapiens)
  - Mitotic G1 phase and G1/S transition (Homo sapiens)
    - G1/S Transition (Homo sapiens)
      - Cyclin E associated events during G1/S transition (Homo sapiens)
        
        Inactivation of Cyclin E:Cdk2 complexes by p27/p21 (Homo sapiens)

Gene expression (Transcription) (Homo sapiens)

- RNA Polymerase II Transcription (Homo sapiens)
  - Generic Transcription Pathway (Homo sapiens)
    - Transcriptional Regulation by TP53 (Homo sapiens)
      - TP53 Regulates Transcription of Cell Cycle Genes (Homo sapiens)
        
        TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest (Homo sapiens)
        
        Inactivation of Cyclin E:Cdk2 complexes by p27/p21 (Homo sapiens)

General

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Inactivation of Cyclin E:Cdk2 complexes by p27/p21

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During G1, the activity of cyclin-dependent kinases (CDKs) is controlled by the CDK inhibitors (CKIs) CDKN1A (p21) and CDKN1B (p27), thereby preventing premature entry into S phase (see Guardavaccaro and Pagano, 2006). The efficient recognition and ubiquitination of p27 by the SCF (Skp2) complex requires the formation of a trimeric complex containing p27 and cyclin E/A:Cdk2.

Literature References

PubMed ID	Title	Journal	Year
10323868	Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation Montagnoli, A, Fiore, F, Eytan, E, Carrano, AC, Draetta, GF, Hershko, A, Pagano, M	Genes Dev	1999
8242751	The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Harper, JW, Adami, GR, Wei, N, Keyomarsi, K, Elledge, SJ	Cell	1993
16262255	Ubiquitination of p21Cip1/WAF1 by SCFSkp2: substrate requirement and ubiquitination site selection Wang, W, Nacusi, L, Sheaff, RJ, Liu, X	Biochemistry	2005