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Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects
Stable Identifier
R-HSA-9659787
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Disease (Homo sapiens)
Diseases of mitotic cell cycle (Homo sapiens)
Aberrant regulation of mitotic cell cycle due to RB1 defects (Homo sapiens)
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects (Homo sapiens)
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RB1 protein, also known as pRB or retinoblastoma protein, is a nuclear protein that plays a major role in the regulation of the G1/S transition during mitotic cell cycle in multicellular eukaryotes. RB1 performs this function by binding to activating E2Fs (E2F1, E2F2 and E2F3), and preventing transcriptional activation of E2F1/2/3 target genes, which include a number of genes involved in DNA synthesis. RB1 binds E2F1/2/3 through the so-called pocket region, which is formed by two parts, pocket domain A (amino acid residues 373-579) and pocket domain B (amino acid residues 640-771). Besides intact pocket domains, RB1 requires an intact nuclear localization signal (NLS) at its C-terminus (amino acid residues 860-876) to be fully functional (reviewed by Classon and Harlow 2002, Dick 2007). Functionally characterized RB1 mutations mostly affect pocket domains A and B and the NLS. RB1 mutations reported in cancer are, however, scattered over the entire RB1 coding sequence and the molecular consequences of the vast majority of these mutations have not been studied (reviewed by Dick 2007).
Many viral oncoproteins inactivate RB1 by competing with E2F1/2/3 for binding to the pocket region of RB1. RB1 protein is targeted by the large T antigen of the Simian virus 40 (SV40), the adenoviral E1A protein, and the E7 protein of oncogenic human papilloma viruses (HPVs) (reviewed by Classon and Harlow 2002).
Literature References
PubMed ID
Title
Journal
Year
12459729
The retinoblastoma tumour suppressor in development and cancer
Classon, M
,
Harlow, E
Nat. Rev. Cancer
2002
17854503
Structure-function analysis of the retinoblastoma tumor suppressor protein - is the whole a sum of its parts?
Dick, FA
Cell Div
2007
Participants
Events
Defective translocation of RB1 mutants to the nucleus
(Homo sapiens)
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)
(Homo sapiens)
Participates
as an event of
Aberrant regulation of mitotic cell cycle due to RB1 defects (Homo sapiens)
Disease
Name
Identifier
Synonyms
cancer
DOID:162
malignant tumor, malignant neoplasm, primary cancer
Authored
Orlic-Milacic, M (2020-05-07)
Reviewed
Dick, FA (2020-05-17)
Created
Orlic-Milacic, M (2019-09-05)
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