Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Cdkn1a. (This text reflects annotations as of Tuesday, May 21, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin-CDK2 or -CDK4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. This protein can interact with proliferating cell nuclear antigen (PCNA), a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of CDK2, and may be instrumental in the execution of apoptosis following caspase activation. Multiple alternatively spliced variants have been found for this gene. [provided by RefSeq, Nov 2010]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Cdkn1a
  • participates in the following biological processes:
    • cell cycle arrest ^[2]
    • mitotic cell cycle arrest ^[9]
    • negative regulation of cyclin-dependent protein serine/threonine kinase activity ^[8]
    • regulation of cell cycle ^[3]
  • performs the following molecular functions:
    • cyclin binding ^[12]
    • cyclin-dependent protein serine/threonine kinase inhibitor activity ^[8]
  • is located in the following cellular components:
    • cytoplasm ^[4]
    • cytosol ^[7]
    • nucleus ^{[4, 13]}
• The gene product of Cdkn1a has been shown to bind to the gene products of Ccnd1, Cdk1, Cdk2, Cdk4, Gadd45g, Hspa8. ^{[1, 3, 12, 13]} Researchers have inferred, based on physical interactions, that the gene product of Cdkn1a
  • performs the following molecular functions:
  • is located in the following cellular components:
    • cyclin-dependent protein kinase holoenzyme complex ^[13]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Cdkn1a
  • participates in the following biological processes:
    • negative regulation of apoptotic process ^[10]
    • negative regulation of cell proliferation ^{[6, 11]}
    • negative regulation of gene expression ^[5]
    • positive regulation of programmed cell death ^[6]
    • regulation of cyclin-dependent protein serine/threonine kinase activity ^[5]
    • regulation of DNA biosynthetic process ^[5]
    • regulation of mitotic cell cycle ^[5]
    • regulation of protein import into nucleus, translocation ^[5]
    • response to DNA damage stimulus ^[10]
    • response to UV ^[10]
• Researchers have inferred, based on genetic interactions, that the gene product of Cdkn1a
  • participates in the following biological processes:
    • positive regulation of B cell proliferation based on interactions with Casp3 ^[13]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Cdkn1a:
  • participates in the following biological processes:
    • cell cycle arrest
    • cellular response to extracellular stimulus
    • cellular response to ionizing radiation
    • cellular senescence
    • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
    • G1/S transition of mitotic cell cycle
    • G2/M transition of mitotic cell cycle
    • negative regulation of apoptotic process
    • negative regulation of cell growth
    • negative regulation of cell proliferation
    • negative regulation of phosphorylation
    • positive regulation of fibroblast proliferation
    • positive regulation of reactive oxygen species metabolic process
    • response to DNA damage stimulus
  • performs the following molecular functions:
    • cyclin-dependent protein kinase activating kinase activity
    • protein complex binding
  • is located in the following cellular components:
    • cyclin-dependent protein kinase holoenzyme complex
    • cytoplasm
    • nucleus
    • PCNA-p21 complex

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Cdkn1a indicates that it:
  • participates in the following biological processes:
    • cell cycle
    • phosphorylation
  • performs the following molecular functions:
    • kinase activity
    • metal ion binding
    • protein kinase inhibitor activity

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References

1. Azam N et al. (2001) Interaction of CR6 (GADD45gamma ) with proliferating cell nuclear antigen impedes negative growth control. J Biol Chem, 276:2766-74. (PubMed:11022036)
2. Chen PL et al. (2005) Inactivation of CtIP Leads to Early Embryonic Lethality Mediated by G1 Restraint and to Tumorigenesis by Haploid Insufficiency. Mol Cell Biol, 25:3535-42. (PubMed:15831459)
3. Diehl JA et al. (2003) Hsc70 regulates accumulation of cyclin D1 and cyclin D1-dependent protein kinase. Mol Cell Biol, 23:1764-74. (PubMed:12588994)
4. Ilan N et al. (2001) Pecam-1 is a modulator of stat family member phosphorylation and localization: lessons from a transgenic mouse. Dev Biol, 232:219-32. (PubMed:11254359)
5. Jaime M et al. (2002) The p21(Cip1) protein, a cyclin inhibitor, regulates the levels and the intracellular localization of CDC25A in mice regenerating livers. Hepatology, 35:1063-71. (PubMed:11981756)
6. Kwon YH et al. (2003) The Cdk inhibitor p21 is required for necrosis, but it inhibits apoptosis following toxin-induced liver injury. J Biol Chem, 278:30348-55. (PubMed:12759355)
7. Laub F et al. (2005) Transcription Factor KLF7 Is Important for Neuronal Morphogenesis in Selected Regions of the Nervous System. Mol Cell Biol, 25:5699-711. (PubMed:15964824)
8. Lazaro JB et al. (2002) Cyclin D-cdk4 activity modulates the subnuclear localization and interaction of MEF2 with SRC-family coactivators during skeletal muscle differentiation. Genes Dev, 16:1792-805. (PubMed:12130539)
9. Nakaya N et al. (2007) noxin, A novel stress-induced gene involved in cell cycle and apoptosis. Mol Cell Biol, 27:5430-44. (PubMed:17515607)
10. Shibue T et al. (2003) Integral role of Noxa in p53-mediated apoptotic response. Genes Dev, 17:2233-8. (PubMed:12952892)
11. Steinman HA et al. (2004) Absence of p21 partially rescues Mdm4 loss and uncovers an antiproliferative effect of Mdm4 on cell growth. Oncogene, 23:303-6. (PubMed:14712235)
12. Vairapandi M et al. (2002) GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with a role in S and G2/M cell cycle checkpoints induced by genotoxic stress. J Cell Physiol, 192:327-38. (PubMed:12124778)
13. Woo M et al. (2003) Caspase-3 regulates cell cycle in B cells: a consequence of substrate specificity. Nat Immunol, 4:1016-22. (PubMed:12970760)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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