RETINOBLASTOMA-RELATED PROTEIN PRB2 P130 AND ITS BINDING TO THE B-MYBPROMOTER INCREASE DURING HUMAN NEUROBLASTOMA-DIFFERENTIATION/

Neuroblastoma cells can undergo neural differentiation upon treatment with a variety of chemical inducers and growth factors. During this pr ocess, many cell cycle-related genes are downregulated while different iation-specific genes are triggered. The retinoblastoma family protein s, pRb, p107, and pRb2/p130, are involved in transcriptional repressio n of proliferation genes, mainly through their interaction with the E2 F transcription factors. We report that pRb2/p130 expression levels in creased during differentiation of neuroblastoma cell line LAN-5. On th e other hand, both pRb and p107 decreased and underwent progressive de phosphorylation at late differentiation times. The expression of B-myb and c-myb, two targets of the retinoblastoma family proteins, were do wnregulated in association with the increase of pRb2/p130, which was d etected as the major component of the complex with E2F on the E2F site of the B-myb promoter in differentiated cells. Interestingly, E2F4, a preferential partner of p107 and pRb2/p130, was upregulated and under went changes in cellular localization during differentiation. In concl usion, our data suggest a major role of pRb2/p130 in the regulation of B-myb promoter during neural differentiation despite the importance o f cofactors in modulating the function of the retinoblastoma family pr oteins. (C) 1997 Wiley-Liss, Inc.