PMC:2948432 / 2693-4468
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/2948432","sourcedb":"PMC","sourceid":"2948432","source_url":"https://www.ncbi.nlm.nih.gov/pmc/2948432","text":"A number of signal transduction and cell cycle regulatory pathways have been implicated in the etiology and progression of melanoma, including the retinoblastoma (RB1) and p44/42 mitogen-activated protein kinase (MAPK) pathways. A key region is 9p21.3, which contains the CDKN2A and CDKN2B genes. These genes encode three separate tumor suppressor proteins. CDKN2A encodes both CDKN2A and, using a separate first exon and alternate reading frame, P14ARF. Although both transcripts use exons 2 and 3 of CDKN2A, the CDKN2A and P14ARF proteins share no homology at the amino acid level and have distinct tumor suppressor functions in the RB1 and TP53 pathways; CDKN2B encodes CDKN2B, which has its own open reading frame (Sharpless and DePinho,1999; Weber et al.,1999). The CDKN2A protein controls passage through the G1 checkpoint of the cell cycle by inhibiting the phosphorylation of the RB1 protein (Roussel,1999) and of the three tumor suppressors at this locus is the one longest recognized to have a significant role in melanoma. It is known to play a key role in normal melanocyte senescence (Ha et al.,2008). The P14ARF protein acts on the TP53 cell cycle control pathway by interaction with the human double minute (HDM2) protein to stabilize TP53 and allow cell cycle arrest at the G1/G2 phase (Weber et al.,1999). CDKN2A was identified first as a tumor suppressor gene commonly deleted/mutated in tumor cell lines (Kamb et al.,1994a) and subsequently its role as a high-risk susceptibility gene in melanoma families was elucidated (Kamb et al.,1994b). Germline mutations have been identified in ∼20% of tested melanoma families (Goldstein and Tucker,2001; Bishop et al.,2002). Some mutations impact on CDKN2A protein alone, some on P14ARF, and some on both proteins.","tracks":[{"project":"2_test","denotations":[{"id":"20140953-10072356-43951705","span":{"begin":741,"end":745},"obj":"10072356"},{"id":"20140953-10559859-43951706","span":{"begin":760,"end":764},"obj":"10559859"},{"id":"20140953-10498883-43951707","span":{"begin":909,"end":913},"obj":"10498883"},{"id":"20140953-18604170-43951708","span":{"begin":1108,"end":1112},"obj":"18604170"},{"id":"20140953-10559859-43951709","span":{"begin":1316,"end":1320},"obj":"10559859"},{"id":"20140953-11708953-43951712","span":{"begin":1659,"end":1663},"obj":"11708953"},{"id":"20140953-12072543-43951713","span":{"begin":1679,"end":1683},"obj":"12072543"}],"attributes":[{"subj":"20140953-10072356-43951705","pred":"source","obj":"2_test"},{"subj":"20140953-10559859-43951706","pred":"source","obj":"2_test"},{"subj":"20140953-10498883-43951707","pred":"source","obj":"2_test"},{"subj":"20140953-18604170-43951708","pred":"source","obj":"2_test"},{"subj":"20140953-10559859-43951709","pred":"source","obj":"2_test"},{"subj":"20140953-11708953-43951712","pred":"source","obj":"2_test"},{"subj":"20140953-12072543-43951713","pred":"source","obj":"2_test"}]},{"project":"0_colil","denotations":[{"id":"20140953-10072356-957357","span":{"begin":741,"end":745},"obj":"10072356"},{"id":"20140953-10559859-957358","span":{"begin":760,"end":764},"obj":"10559859"},{"id":"20140953-10498883-957359","span":{"begin":909,"end":913},"obj":"10498883"},{"id":"20140953-18604170-957360","span":{"begin":1108,"end":1112},"obj":"18604170"},{"id":"20140953-10559859-957361","span":{"begin":1316,"end":1320},"obj":"10559859"},{"id":"20140953-11708953-957364","span":{"begin":1659,"end":1663},"obj":"11708953"},{"id":"20140953-12072543-957365","span":{"begin":1679,"end":1683},"obj":"12072543"}],"attributes":[{"subj":"20140953-10072356-957357","pred":"source","obj":"0_colil"},{"subj":"20140953-10559859-957358","pred":"source","obj":"0_colil"},{"subj":"20140953-10498883-957359","pred":"source","obj":"0_colil"},{"subj":"20140953-18604170-957360","pred":"source","obj":"0_colil"},{"subj":"20140953-10559859-957361","pred":"source","obj":"0_colil"},{"subj":"20140953-11708953-957364","pred":"source","obj":"0_colil"},{"subj":"20140953-12072543-957365","pred":"source","obj":"0_colil"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#c0ec93","default":true},{"id":"0_colil","color":"#ec93da"}]}]}}