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Titolo:
Direct trans-activation of the human cyclin D2 gene by the oncogene product Tax of human T-cell leukemia virus type I
Autore:
Huang, YP; Ohtani, K; Iwanaga, R; Matsumura, Y; Nakamura, M;
Indirizzi:
Tokyo Med & Dent Univ, Human Gene Sci Ctr, Bunkyo Ku, Tokyo 1138510, JapanTokyo Med & Dent Univ Tokyo Japan 1138510 unkyo Ku, Tokyo 1138510, Japan
Titolo Testata:
ONCOGENE
fascicolo: 9, volume: 20, anno: 2001,
pagine: 1094 - 1102
SICI:
0950-9232(20010301)20:9<1094:DTOTHC>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN LYMPHOCYTES-T; EXPRESSION; PROTEIN; E2F; CANCER; LINES; DIFFERENTIATION; ESTABLISHMENT; TRANSCRIPTION; ACCUMULATION;
Keywords:
cell cycle; CREB; HTLV-I; NF-kappa B; tax; cyclin D2;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Ohtani, K Tokyo Med & Dent Univ, Human Gene Sci Ctr, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138510, Japan Tokyo Med & Dent Univ 1-5-45 Yushima Tokyo Japan 1138510 Japan
Citazione:
Y.P. Huang et al., "Direct trans-activation of the human cyclin D2 gene by the oncogene product Tax of human T-cell leukemia virus type I", ONCOGENE, 20(9), 2001, pp. 1094-1102

Abstract

Cyclins are one of the pivotal determinants regulating cell cycle progression. We previously reported that the trans-activator Tax of human T-cell leukemia virus type I(HTLV-I) induces endogenous cyclin D2 expression along with cell cycle progression in a resting human T-cell line, Kit 225, suggesting a role of cyclin D2 in Tax-mediated cell cycle progression, The cyclin D2 gene has a typical E2F binding element, raising the possibility that induction of cyclin D2 expression is a consequence of cell cycle progression. In this study, we examined the role and molecular mechanism of induction ofthe endogenous human cyclin D2 gene by Tax. Introduction of p19(INK4d), a cyclin dependent kinase (CDK) inhibitor of the INK4 family specific for D-type CDK, inhibited Tax-mediated activation of E2F, indicating requirement of D-type CDK in Tax-mediated activation of E2F, Previously indicated E2F binding element and, two NF-kappaB-like binding elements in the 1.6 kbp cyclin D2 promoter fragment had little, if any, effect on responsiveness to Tax,We found that trans-activation of the cyclin D2 promoter by Tax was mainlymediated by a newly identified NF-kappaB-like element with auxiliary contribution of a CRE-like element residing in sequences downstream of -444 which were by themselves sufficient for transactivation by Tax. These results indicate that Tax directly trans-activates the cyclin D2 gene, resulting in growth promotion and perhaps leukemogenesis through activation of D-type CDK.

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Documento generato il 29/11/20 alle ore 01:00:29