RGD Reference Report - The degradation of cell cycle regulators by SKP2/CKS1 ubiquitin ligase is genetically controlled in rodent liver cancer and contributes to determine the susceptibility to the disease. - Rat Genome Database

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The degradation of cell cycle regulators by SKP2/CKS1 ubiquitin ligase is genetically controlled in rodent liver cancer and contributes to determine the susceptibility to the disease.

Authors: Calvisi, DF  Pinna, F  Ladu, S  Muroni, MR  Frau, M  Demartis, I  Tomasi, ML  Sini, M  Simile, MM  Seddaiu, MA  Feo, F  Pascale, RM 
Citation: Calvisi DF, etal., Int J Cancer. 2009 Jun 16.
RGD ID: 2315050
Pubmed: PMID:19533683   (View Abstract at PubMed)
DOI: DOI:10.1002/ijc.24650   (Journal Full-text)

Previous work showed a genetic control of cell cycle deregulation during hepatocarcinogenesis. We now evaluated in preneoplastic lesions, dysplastic nodules and hepatocellular carcinoma (HCC), chemically induced in genetically susceptible F344 and resistant Brown Norway (BN) rats, the role of cell cycle regulating proteins in the determination of a phenotype susceptible to HCC development. p21(WAF1), p27(KIP1), p57(KIP2) and p130 mRNA levels increased in fast growing lesions of F344 rats. Lower/no increases occurred in slowly growing lesions of BN rats. A similar behavior of RassF1A mRNA was previously found in the 2 rat strains. However, p21(WAF1), p27(KIP1), p57(KIP), p130 and RassF1A proteins exhibited no change/low increase in the lesions of F344 rats and consistent rise in dysplastic nodules and HCC of BN rats. Increase in Cks1-Skp2 ligase and ubiquitination of cell cycle regulators occurred in F344 but not in BN rat lesions, indicating that posttranslational modifications of cell cycle regulators are under genetic control and contribute to determine a phenotype susceptible to HCC. Moreover, proliferation index of 60 human HCCs was inversely correlated with protein levels but not with mRNA levels of P21(WAF1), P27(KIP1), P57(KIP2) and P130, indicating a control of human HCC proliferation by posttranslational modifications of cell cycle regulators. (c) 2009 UICC.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Liver Neoplasms disease_progressionISOCdkn1b (Rattus norvegicus)2315050; 2315050mRNA:increased expression:liver (rat)RGD 
Experimental Liver Neoplasms disease_progressionISOCdkn1c (Rattus norvegicus)2315050; 2315050mRNA:increased expression:liver (rat)RGD 
Experimental Liver Neoplasms disease_progressionIEP 2315050; 2315050; 2315050; 2315050mRNA:increased expression:liver (rat)RGD 
Experimental Liver Neoplasms severityIAGP 2315050compared to BN strainRGD 
Experimental Liver Neoplasms disease_progressionISOKras (Rattus norvegicus)2315050; 2315050mRNA:increased expression:liver (rat)RGD 
Experimental Liver Neoplasms disease_progressionISOPlcl1 (Rattus norvegicus)2315050; 2315050mRNA:increased expression:liver (rat)RGD 
hepatocellular carcinoma  ISOSkp2 (Rattus norvegicus)2315050; 2315050protein:increased expression:liverRGD 
hepatocellular carcinoma  IEP 2315050protein:increased expression:liverRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Cdkn1a  (cyclin-dependent kinase inhibitor 1A)
Cdkn1b  (cyclin-dependent kinase inhibitor 1B)
Cdkn1c  (cyclin-dependent kinase inhibitor 1C)
Kras  (KRAS proto-oncogene, GTPase)
Plcl1  (phospholipase C-like 1)
Rassf1  (Ras association domain family member 1)
Rbl2  (RB transcriptional corepressor like 2)
Skp2  (S-phase kinase associated protein 2)

Genes (Mus musculus)
Cdkn1b  (cyclin dependent kinase inhibitor 1B)
Cdkn1c  (cyclin dependent kinase inhibitor 1C)
Kras  (Kirsten rat sarcoma viral oncogene homolog)
Plcl1  (phospholipase C-like 1)
Skp2  (S-phase kinase-associated protein 2)

Genes (Homo sapiens)
CDKN1B  (cyclin dependent kinase inhibitor 1B)
CDKN1C  (cyclin dependent kinase inhibitor 1C)
KRAS  (KRAS proto-oncogene, GTPase)
PLCL1  (phospholipase C like 1 (inactive))
SKP2  (S-phase kinase associated protein 2)

Strains
F344/Crli  (NA)


Additional Information