The Pbx family of proteins is strongly upregulated by a post-transcriptional mechanism during retinoic acid-induced differentiation of P19 embryonal carcinoma cells.
Retinoic acid (RA) induces expression of genes encoding the Hox family of transcription factors, whose differential expression orchestrates developmental programs specifying anterior-posterior structures during embryogenesis. Hox proteins bind DNA as monomers and heterodimers with Pbx proteins. Here we show that RA upregulates Pbx protein abundance coincident with transcriptional activation of Hox genes in P19 embryonal carcinoma cells undergoing neuronal differentiation. However, in contrast to Hox induction, Pbx upregulation is predominantly a result of post-transcriptional mechanisms. Interestingly, Pbx1, Pbx2, and Pbx3 exhibit different profiles of upregulation, suggesting possible functional divergence. The parallel upregulation of Pbx and Hox proteins in this model suggests an important role for transcriptional control by Pbx-Hox heterodimers during neurogenesis, and argues for precise control by RA.
Knoepfler
P S
PS
Department of Pathology, University of California, School of Medicine, La Jalla 92093, USA.
Kamps
M P
MP
D000818:Animals; D018236:Carcinoma, Embryonal; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016716:PC12 Cells; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D051381:Rats; D015533:Transcriptional Activation; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D004967:Estrogens; D018398:Homeodomain Proteins; C090465:PBX2 protein, human; C490382:Pbx2 protein, mouse; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; C083400:PBX1 protein, human; C090466:proto-oncogene protein Pbx3; D014212:Tretinoin; D003907:Dexamethasone