| Predicate | Object |
|---|---|
| rdf:type | |
| http://www.biopax.org/relea... | |
| http://www.biopax.org/relea... |
Cyclin-dependent kinase inhibitor 1
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| http://www.biopax.org/relea... |
CDN1A_MOUSE
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| http://www.biopax.org/relea... | |
| http://www.biopax.org/relea... |
CDK-interacting protein 1,
Melanoma differentiation-associated protein,
p21
|
| http://www.biopax.org/relea... |
FUNCTION: May be the important intermediate by which p53/TP53 mediates its role as an inhibitor of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin- dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D- CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex (By similarity). SUBUNIT: Interacts with MKRN1. Interacts with PSMA3. Interacts with PCNA. Component of the ternary complex, cyclin D-CDK4-CDKN1A. Interacts (via its N-terminal domain) with CDK4; the interaction promotes the assembly of the cyclin D-CDK4 complex, its nuclear translocation and promotes the cyclin D-dependent enzyme activity of CDK4 (By similarity). SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By similarity). INDUCTION: By p53, mezerein (antileukemic compound) and interferon beta. DOMAIN: The C-terminal is required for nuclear localization of the cyclin D-CDK4 complex (By similarity). DOMAIN: The PIP-box K+4 motif mediates both the interaction with PCNA and the recuitment of the DCX(DTL) complex: while the PIP-box interacts with PCNA, the presence of the K+4 submotif, recruits the DCX(DTL) complex, leading to its ubiquitination (By similarity). PTM: Phosphorylation of Thr-140 or Ser-141 impairs binding to PCNA. Phosphorylation at Ser-112 by GSK3-beta enhances ubiquitination by the DCX(DTL) complex (By similarity). PTM: Ubiquitinated by MKRN1; leading to polyubiquitination and 26S proteasome-dependent degradation. Ubiquitinated by the DCX(DTL) complex, also named CRL4(CDT2) complex, leading to its degradation during S phase or following UV irradiation. Ubiquitination by the DCX(DTL) complex is essential to control replication licensing and is PCNA-dependent: interacts with PCNA via its PIP-box, while the presence of the containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to its degradation (By similarity). SIMILARITY: Belongs to the CDI family. GENE SYNONYMS: Cip1 Waf1. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.
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