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Literature summary for 2.7.11.22 extracted from

  • Aggarwal, P.; Vaites, L.P.; Kim, J.K.; Mellert, H.; Gurung, B.; Nakagawa, H.; Herlyn, M.; Hua, X.; Rustgi, A.K.; McMahon, S.B.; Diehl, J.A.
    Nuclear cyclin D1/CDK4 kinase regulates CUL4 expression and triggers neoplastic growth via activation of the PRMT5 methyltransferase (2010), Cancer Cell, 18, 329-340.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
cyclin D1 CDK4 is dependent on Mus musculus
cyclin D1 CDK4 is dependent on Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
overexpression of wild-type cyclin D1/CDK4 in HeLa cells, coexpression of cyclin D1 or cyclin D1T286A along with either CDK4 or CDK4(K35M) in HeLa cells Homo sapiens

Protein Variants

Protein Variants Comment Organism
K35m site-directed mutagenesis of CDK4 Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
nucleus
-
Homo sapiens 5634
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + MEP50 protein Mus musculus a PRMT5 co-regulatory factor ADP + MEP50 phosphoprotein
-
?
ATP + MEP50 protein Homo sapiens a PRMT5 co-regulatory factor ADP + MEP50 phosphoprotein
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Mus musculus
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
HeLa cell and other cancer cell lines Homo sapiens
-
lymphoma cell primary tumors of a mouse lymphoma model Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + MEP50 protein a PRMT5 co-regulatory factor Mus musculus ADP + MEP50 phosphoprotein
-
?
ATP + MEP50 protein a PRMT5 co-regulatory factor Homo sapiens ADP + MEP50 phosphoprotein
-
?
ATP + MEP50 protein a PRMT5 co-regulatory factor, purified recombinant PRMT5/MEP50 produced in Sf9 cells or HeLa cells, phosphorylation of Thr5 and perhaps Ser264 by CDK4 Homo sapiens ADP + MEP50 phosphoprotein
-
?

Synonyms

Synonyms Comment Organism
CDK4 kinase
-
Mus musculus
CDK4 kinase
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
Mus musculus
ATP
-
Homo sapiens

General Information

General Information Comment Organism
metabolism the primary cellular mechanism that restricts cyclin D1/CDK4 activity is cytoplasmic, ubiquitin-mediated degradation of cyclin D1 during S-phase. Mutations that disrupt this event, via within the cyclin D1 degron or inactivating the cyclin D1 E3 ligase, Fbx4, directly contribute to neoplastic growth Mus musculus
metabolism the primary cellular mechanism that restricts cyclin D1/CDK4 activity is cytoplasmic, ubiquitin-mediated degradation of cyclin D1 during S-phase. Mutations that disrupt this event, via within the cyclin D1 degron or inactivating the cyclin D1 E3 ligase, Fbx4, directly contribute to neoplastic growth Homo sapiens
physiological function nuclear cyclin D1/CDK4-dependent repression of CUL4A and CUL4B, encoding scaffolding proteins for the E3 ligase that directs CDT1 degradation during S-phase, the repression requires S-phase accumulation of catalytically active cyclin D1/CDK4, molecular mechanism, overview. Cyclin D1/CDK4 can increase histone methyltransferase activity of PRMT5/MEP50, a PRMT5 co-regulatory factor, through phosphorylation of Thr5 and perhaps through Ser264, and increased PRMT5 activity mediates key events associated with cyclin D1-dependent neoplastic growth including CUL4 repression, CDT1 overexpression, and DNA re-replication. Cyclin D1T286A/CDK4 regulates PRMT5 methyltransferase activity via MEP50 phosphorylation, overview Homo sapiens
physiological function nuclear cyclin D1/CDK4-dependent repression of CUL4A and CUL4B, encoding scaffolding proteins for the E3 ligase that directs CDT1 degradation during S-phase, the repression requires S-phase accumulation of catalytically active cyclin D1/CDK4, molecular mechanism, overview. Phosphorylation of MEP50, a PRMT5 co-regulatory factor, by CDK4 increases PRMT5/MEP50 activity, and increased PRMT5 activity mediates key events associated with cyclin D1-dependent neoplastic growth including CUL4 repression, CDT1 overexpression, and DNA re-replication Mus musculus