Retinoblastoma-related protein pRb2/p130 and its binding to the B-myb promoter increase during human neuroblastoma differentiation

• Published in: Journal of cellular biochemistry 1997-12, Vol.67 (3), p.297-303
• Main Authors: Raschellà, Giuseppe, Tanno, Barbara, Bonetto, Francesco, Amendola, Roberto, Battista, Tullio, De Luca, Antonio, Giordano, Antonio, Paggi, Marco G.
• Format: Article
• Language: English
• Subjects: B-myb; c-myb; Carrier Proteins; Cell Cycle Proteins; Cell Differentiation; Cell Nucleus - chemistry; Cytoplasm - chemistry; differentiation; DNA, Neoplasm - metabolism; DNA-Binding Proteins - analysis; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; E2F; E2F Transcription Factors; E2F4 Transcription Factor; Gene Expression Regulation, Neoplastic - genetics; Humans; Neurites - chemistry; neuroblastoma; Neuroblastoma - genetics; Neuroblastoma - metabolism; Neuroblastoma - pathology; Neurons - cytology; Neurons - metabolism; Nuclear Proteins - biosynthesis; Nuclear Proteins - metabolism; p107; Phosphoproteins - biosynthesis; Phosphoproteins - metabolism; pRb; pRb2/p130; promoter; Promoter Regions, Genetic - genetics; Proteins; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins c-myb; retinoblastoma family; Retinoblastoma Protein - biosynthesis; Retinoblastoma-Binding Protein 1; Retinoblastoma-Like Protein p107; Retinoblastoma-Like Protein p130; Trans-Activators - biosynthesis; Transcription Factor DP1; Transcription Factors - analysis; Transcription Factors - biosynthesis; Transcription Factors - genetics; Tumor Cells, Cultured
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/(SICI)1097-4644(19971201)67:3<297::AID-JCB2>3.0.CO;2-R

Neuroblastoma cells can undergo neural differentiation upon treatment with a variety of chemical inducers and growth factors. During this process, many cell cycle–related genes are downregulated while differentiation‐specific genes are triggered. The retinoblastoma family proteins, pRb, p107, and pRb2/p130, are involved in transcriptional repression of proliferation genes, mainly through their interaction with the E2F transcription factors. We report that pRb2/p130 expression levels increased during differentiation of neuroblastoma cell line LAN‐5. On the other hand, both pRb and p107 decreased and underwent progressive dephosphorylation at late differentiation times. The expression of B‐myb and c‐myb, two targets of the retinoblastoma family proteins, were downregulated in association with the increase of pRb2/p130, which was detected 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 underwent changes in cellular localization during differentiation. In conclusion, our data suggest a major role of pRb2/p130 in the regulation of B‐myb promoter during neural differentiation despite the importance of cofactors in modulating the function of the retinoblastoma family proteins. J. Cell. Biochem. 67:297–303, 1997. © 1997 Wiley‐Liss, Inc.