Title | Cyclin D1-dependent regulation of B-myb activity in early stages of neuroblastoma differentiation |
---|---|
Publication Type | Articolo su Rivista peer-reviewed |
Year of Publication | 2002 |
Authors | Cesi, Vincenzo, Tanno Barbara, Vitali Roberta, Mancini C., Giuffrida M.L., Calabretta B., and Raschellà Giuseppe |
Journal | Cell Death and Differentiation |
Volume | 9 |
Pagination | 1232-1239 |
ISSN | 13509047 |
Keywords | antineoplastic agent, Antineoplastic Agents, article, biological marker, Biological Markers, cell cycle protein, Cell Cycle Proteins, Cell Line, Cell Transformation, controlled study, cyclin A, cyclin D1, DNA binding protein, DNA-Binding Proteins, down regulation, drug effect, enzyme assay, human, human cell, Humans, Immunoprecipitation, luciferase, metabolism, MYBL2 protein, Neoplastic, nerve cell differentiation, Neuroblastoma, neuroblastoma cell, pregnancy specific beta1 glycoprotein, Pregnancy-Specific beta 1-Glycoproteins, priority journal, promoter region, protein analysis, protein degradation, protein expression, protein p21, protein stability, regulatory mechanism, Retinoic acid, rho GTP-Binding Proteins, Rho guanine nucleotide binding protein, Time, Trans-Activators, transactivation, transactivator protein, transcription factor, transcription factor B myb, transcription factor Sp1, Tretinoin, unclassified drug |
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. |
Notes | cited By 20 |
URL | https://www.scopus.com/inward/record.uri?eid=2-s2.0-0036848105&doi=10.1038%2fsj.cdd.4401103&partnerID=40&md5=7d58f8407ca2f2dfdaa179e304082198 |
DOI | 10.1038/sj.cdd.4401103 |
Citation Key | Cesi20021232 |