A novel mechanism for cyclic adenosine 3',5'-monophosphate regulation of gene expression by CREB-binding protein

Kerstin Zanger, Laurie E. Cohen, Koshi Hashimoto, Sally Radovick, Fredric Wondisford

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

The pituitary-specific transcription factor, Pit-1, is necessary to mediate protein kinase A (PKA) regulation of the GH, PRL, and TSH-β subunit genes in the pituitary. Since these target genes lack classical cAMP DNA response elements (CREs), the mechanism of this regulation was previously unknown. We show that CREB binding protein (CBP), through two cysteine- histidine rich domains (C/H1 and C/H3), specifically and constitutively interacts with Pit-1 in pituitary cells. Pit-1 and CBP synergistically activate the PRL gene after PKA stimulation in a mechanism requiring both an intact Pit-1 amino-terminal and DNA-binding domain. A CBP construct containing the C/H3 domain [amino acids (aa) 1678-2441], but not one lacking the C/H3 domain (aa 1891-2441), is sufficient to mediate this response. Neither construct augments PKA regulation of CRE-containing promoters. Fusion of either CBP fragment to the GAL4 DNA-binding domain transferred complete PKA regulation to a heterologous promoter. These findings provide a mechanism for CREB-independent regulation of gene expression by cAMP.

Original languageEnglish (US)
Pages (from-to)268-275
Number of pages8
JournalMolecular Endocrinology
Volume13
Issue number2
DOIs
StatePublished - Feb 13 1999

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Endocrinology

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