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- Title
Cyclin D1-dependent regulation of B-myb activity in early stages of neuroblastoma differentiation.
- Authors
Cesi, V; Tanno, B; Vitali, R; Mancini, C; Giuffrida, M L; Calabretta, B; Raschellà, G
- Abstract
Levels of the transcription factor B-myb must be down-regulated to allow terminal differentiation of neuroectodermal cells and yet its constitutive expression induces early markers of neural differentiation. Thus, we investigated potential mechanisms of enhanced B-myb activity in early stages of neural differentiation. We report here that B-myb expression does not decrease, cyclin A and Sp1 levels remain constant while p21 levels increase continuously upon retinoic acid-induced differentiation of the LAN-5 neuroblastoma cell line. In contrast, cyclin D1 expression is down-regulated at the onset of the differentiative process by protein destabilization. Luciferase assays of promoter activity indicate that B-myb-dependent transactivation is enhanced in LAN-5 cells treated with retinoic acid (RA) for 24 h. The enhancement is independent from cyclin A but is suppressed by a degradation-resistant mutant form of cyclin D1. The importance of cyclin D1 in controlling B-myb activity is further suggested by co-immunoprecipitation experiments, showing that the amount of cyclin D1 co-immunoprecipitated with B-myb decreased after RA treatment. Thus, B-myb may play an active role in the early stages of differentiation when its transactivation activity is enhanced as a consequence of cyclin D1 down-modulation.Cell Death and Differentiation (2002) 9, 1232–1239. doi:10.1038/sj.cdd.4401103
- Subjects
TRANSCRIPTION factors; NEUROBLASTOMA; CELL differentiation
- Publication
Cell Death & Differentiation, 2002, Vol 9, Issue 11, p1232
- ISSN
1350-9047
- Publication type
Article
- DOI
10.1038/sj.cdd.4401103