Oct-1 functions as a transactivator in the hormonal induction of beta-casein gene expression

Mol Cell Biochem. 2009 Aug;328(1-2):93-9. doi: 10.1007/s11010-009-0078-5. Epub 2009 Mar 6.

Abstract

The ubiquitous transcription factor Oct-1 is involved in the hormonal regulation of the transcription of the major milk protein beta-casein through an interaction with the prolactin receptor, the STAT-5, and the glucocorticoid receptor (GR). In this study, this interaction was further demonstrated using Oct-1-deficient cells. In addition, Oct-1 mRNA expression is shown to increase during pregnancy and reach the highest levels during early lactation in mouse mammary gland. In reconstituted COS-7 cells, the endogenous Oct-1 binding activity rapidly increased within 5 min upon the lactogenic hormone treatment, indicating potential post-transcriptional/translational modification of Oct-1 by prolactin and glucocorticoids. Furthermore, STAT-5B was as effective as STAT-5A in the interaction with Oct-1 during hormonal induction, and a GR mutant, which carries mutations at multiple potential phosphorylation sites, functioned similarly to the wild-type GR, indicating that these phosphorylation sites may not be involved in the interaction of GR with Oct-1 on the beta-casein gene promoter.

MeSH terms

  • Animals
  • COS Cells
  • Caseins / biosynthesis*
  • Chlorocebus aethiops
  • Female
  • Glucocorticoids / pharmacology
  • Hormones / pharmacology*
  • Mammary Glands, Animal / metabolism
  • Mammary Glands, Animal / physiology
  • Mice
  • Mice, Inbred C57BL
  • Octamer Transcription Factor-1 / physiology*
  • Pregnancy
  • Prolactin / pharmacology
  • Promoter Regions, Genetic
  • RNA, Messenger / analysis
  • Receptors, Glucocorticoid / metabolism
  • Receptors, Prolactin / metabolism
  • STAT5 Transcription Factor / metabolism
  • Trans-Activators / physiology*
  • Transcriptional Activation / drug effects*

Substances

  • Caseins
  • Glucocorticoids
  • Hormones
  • Octamer Transcription Factor-1
  • RNA, Messenger
  • Receptors, Glucocorticoid
  • Receptors, Prolactin
  • STAT5 Transcription Factor
  • Trans-Activators
  • Prolactin