Retinoblastoma-related protein pRb2/p130 and its binding to the B-myb promoter increase during human neuroblastoma differentiation.
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.
Raschellà
G
G
Section of Toxicology and Biomedical Sciences, Ente Nuove Tecnologie Energia e Ambiente (ENEA), Rome, Italy.
Tanno
B
B
Bonetto
F
F
Amendola
R
R
Battista
T
T
De Luca
A
A
Giordano
A
A
Paggi
M G
MG
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D004273:DNA, Neoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D050684:E2F Transcription Factors; D050704:E2F4 Transcription Factor; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D016501:Neurites / Q000737:chemistry; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000378:metabolism; D010750:Phosphoproteins / Q000096:biosynthesis / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011506:Proteins; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D020598:Proto-Oncogene Proteins c-myb; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D015534:Trans-Activators / Q000096:biosynthesis; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050704:E2F4 Transcription Factor; C493762:E2F4 protein, human; C064352:MYBL2 protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; C493844:RBL1 protein, human; C493837:RBL2 protein, human; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D015534:Trans-Activators; D050680:Transcription Factor DP1; D014157:Transcription Factors