Cyclin D1-dependent regulation of B-myb activity in early stages of neuroblastoma differentiation

V. Cesi, B. Tanno, R. Vitali, C. Mancini, M.L. Giuffrida, B. Calabretta, G. Raschellà

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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.
Original languageEnglish
Pages (from-to)1232 - 1239
Number of pages8
JournalCell Death and Differentiation
Volume9
Issue number11
DOIs
Publication statusPublished - 2002
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Cesi, V., Tanno, B., Vitali, R., Mancini, C., Giuffrida, M. L., Calabretta, B., & Raschellà, G. (2002). Cyclin D1-dependent regulation of B-myb activity in early stages of neuroblastoma differentiation. Cell Death and Differentiation, 9(11), 1232 - 1239. https://doi.org/10.1038/sj.cdd.4401103