Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Carrier Proteins*
-
Cell Cycle Proteins*
-
Cell Differentiation
-
Cell Nucleus / chemistry
-
Cytoplasm / chemistry
-
DNA, Neoplasm / metabolism
-
DNA-Binding Proteins / analysis
-
DNA-Binding Proteins / biosynthesis
-
DNA-Binding Proteins / genetics*
-
E2F Transcription Factors
-
E2F4 Transcription Factor
-
Gene Expression Regulation, Neoplastic / genetics
-
Humans
-
Neurites / chemistry
-
Neuroblastoma / genetics
-
Neuroblastoma / metabolism*
-
Neuroblastoma / pathology*
-
Neurons / cytology*
-
Neurons / metabolism
-
Nuclear Proteins / biosynthesis
-
Nuclear Proteins / metabolism
-
Phosphoproteins / biosynthesis
-
Phosphoproteins / metabolism*
-
Promoter Regions, Genetic / genetics*
-
Proteins*
-
Proto-Oncogene Proteins / biosynthesis
-
Proto-Oncogene Proteins c-myb
-
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
Substances
-
Carrier Proteins
-
Cell Cycle Proteins
-
DNA, Neoplasm
-
DNA-Binding Proteins
-
E2F Transcription Factors
-
E2F4 Transcription Factor
-
E2F4 protein, human
-
MYBL2 protein, human
-
Nuclear Proteins
-
Phosphoproteins
-
Proteins
-
Proto-Oncogene Proteins
-
Proto-Oncogene Proteins c-myb
-
RBL1 protein, human
-
RBL2 protein, human
-
Retinoblastoma Protein
-
Retinoblastoma-Binding Protein 1
-
Retinoblastoma-Like Protein p107
-
Retinoblastoma-Like Protein p130
-
Trans-Activators
-
Transcription Factor DP1
-
Transcription Factors