Prolactin signals via Stat5 and Oct-1 to the proximal cyclin D1 promoter.
Prolactin (PRL) modulates proliferation in the mammary gland and other tissues, in part through inducing transcription of cyclin D1, a key regulator of G(1) phase cell cycle progression. We showed previously that PRL, via Jak2, induces binding of Stat5 to a distal GAS site (GAS1) in the cyclin D1 promoter. However, full promoter activity requires additional regions, and in this paper we explored PRL-induced activity at sites other than GAS1. We defined a second PRL-responsive region spanning -254 to -180 that contains a second GAS site (GAS2) and an Oct-1 binding site. Although mutational analysis indicated independence from GAS2, proximal promoter activity remained Stat5-dependent, suggesting alternative mechanisms. EMSA showed that Oct-1 binds the -254 to -180 region and that PRL decreased Oct-1 binding, leading to increased PRL-responsiveness of the proximal cyclin D1 promoter in multiple cell lines. This suggests a role for Oct-1 in PRL-dependent control of cyclin D1 transcription.
Brockman
Jennifer L
JL
Department of Comparative Biosciences, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA.
Schuler
Linda A
LA
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D053614:Janus Kinase 2; D008894:Milk Proteins / Q000378:metabolism*; D009154:Mutation; D050811:Octamer Transcription Factor-1; D011388:Prolactin / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D011518:Proto-Oncogene Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D019938:Cyclin D1; D011388:Prolactin; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2