The retinoblastoma-related Rb2/p130 gene is an effector downstream of AP-2 during neural differentiation.
Rb2/p130, a member of the Retinoblastoma family of growth and tumour suppressor genes, is extensively implicated in the control of cell cycle and differentiation. The minimal promoter region of Rb2/p130 in T98G human glioblastoma cells was identified and its analysis revealed the presence of a KER1 palindromic sequence able to bind the transcription factor AP-2, a regulatory protein that plays a crucial role in ectodermal differentiation. This KER1 site interacted in vitro with AP-2, and AP-2 overexpression increased Rb2/p130 transcription and translation. We also found that rat PC12 pheochromocytoma cells, when induced to differentiate by NGF, displayed an increase of AP-2 protein levels and of Rb2/p130 transcription and protein levels. AP-2-transfected PC12 cells displayed enhanced transcription and translation of Rb2/p130 and of the cdk inhibitor p21(WAF1/CIP1), a gene known to be under the control of AP-2, but unable by itself to elicit PC12 differentiation. Overexpression of either AP-2 or Rb2/p130 elicited per se cell differentiation in the absence of NGF, while coexpression of AP-2B, a negative regulator of AP-2 transcriptional activity, inhibited only AP-2-induced differentiation. Altogether, these results indicate that Rb2/p130 is a critical effector of AP-2 in sustaining ectodermal differentiation.
Paggi
M G
MG
Laboratory of Cell Metabolism and Pharmacokinetics, Centre for Experimental Research, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy.
Bonetto
F
F
Severino
A
A
Baldi
A
A
Battista
T
T
Bucci
F
F
Felsani
A
A
Lombardi
D
D
Giordano
A
A
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D004273:DNA, Neoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000502:physiology; D016716:PC12 Cells; D010750:Phosphoproteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011506:Proteins; D051381:Rats; D050717:Retinoblastoma-Like Protein p130; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D011506:Proteins; C493837:RBL2 protein, human; C493839:Rbl2 protein, rat; D050717:Retinoblastoma-Like Protein p130; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase