Stimulation of the murine Uchl1 gene promoter by the B-Myb transcription factor.
It has been reported that human lung cancers frequently overexpress both the ubiquitous cell cycle transcription factor B-myb and the ubiquitin carboxyterminal hydrolase UCHL1, an enzyme whose expression is normally limited to neurons and neuroendocrine cells in the lung. A possible explanation for the co-expression of these markers is that Uchl1 is subject to transcriptional regulation by B-Myb, and in tumors the ectopic expression of UCHL1 is a direct consequence of B-Myb overexpression. We have tested this hypothesis in the mouse model system by cloning the murine Uchl1 promoter and analyzing its regulation by murine B-Myb. Expression of a luciferase reporter gene driven by the Uchl1 promoter was induced by cotransfected B-Myb, but induction was not dependent on the presence of a myb consensus binding site identified in the promoter region. B-Myb induction was dependent on the context of the Uchl1 TATA box, as has been reported for other genes. Transgenic mice expressing a truncated, constitutively active form of B-Myb in the lung epithelium showed elevated expression of UCHL1 protein. We conclude that B-Myb can stimulate expression of the Uchl1 both in cultured cells and in vivo.
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016716:PC12 Cells; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D015534:Trans-Activators / Q000378:metabolism* / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D043222:Ubiquitin Thiolesterase / Q000235:genetics* / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C064352:MYBL2 protein, human; C499306:Mybl2 protein, mouse; D015534:Trans-Activators; D043222:Ubiquitin Thiolesterase