Scholars@Duke publication: Progesterone receptor interacting coregulatory proteins and cross talk with cell signaling pathways.

Progesterone receptor interacting coregulatory proteins and cross talk with cell signaling pathways.

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Edwards, DP; Wardell, SE; Boonyaratanakornkit, V

Published in: J Steroid Biochem Mol Biol

December 2002

Progesterone receptor (PR) is a member of the nuclear receptor family of ligand-dependent transcription activators and is expressed as two different sized proteins from a single gene; PR-A and PR-B. The two PR isoforms are identical in their DNA binding domains (DBD) and C-terminal ligand binding domains (LBD), differing only in the N-terminal domain that is truncated in PR-A. PR also contains two autonomous transcription activation domains (AD), ligand-dependent AF-2 in the C-terminus and constitutive AF-1 in the N-terminus. AF-2 is highly conserved and a family of p160 coactivators that interacts with and mediates the activity of AF-2 has been well characterized. By contrast the N-terminal domain and AF-1 are not conserved and little is known about AF-1 coactivators. The N-terminal domain is functionally important as it is required for full transcription activity of PR and is responsible for the distinct activities of the two PR isoforms, as well as cell and promoter specific functions of PR. This paper describes our efforts to identify PR N-terminal interacting coregulatory proteins. We summarize our work on the role of jun dimerization protein-2 (JDP-2) as an AF-1 coactivator of PR. JDP-2, initially defined as a repressor of jun and other bZIP transcription factors, also functions as a potent PR selective coactivator. JDP-2 lacks an intrinsic activation domain and through association with the DBD, we propose that JDP-2 potentiates AF-1 by recruiting other coactivators independent of AF-2 and p160 pathways. We also discovered that PR contains an SH3 domain interaction motif in the N-terminus that mediates interaction with Src tyrosine kinases and other signaling molecules. This interaction mediates rapid progesterone activation of Src/MAP K signaling pathways and defines a molecular mechanism for some of the rapid non-genomic actions of progesterone.

Duke Scholars

Author Suzanne E Wardell Pharmacology & Cancer Biology

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Published In

J Steroid Biochem Mol Biol

DOI

10.1016/s0960-0760(02)00265-0

ISSN

0960-0760

Publication Date

December 2002

Volume

Issue

1-5

Start / End Page

173 / 186

Location

England

Related Subject Headings

src-Family Kinases
Two-Hybrid System Techniques
Transfection
Transcriptional Activation
Signal Transduction
Sequence Homology, Amino Acid
Repressor Proteins
Receptors, Progesterone
Receptors, Interferon
Proto-Oncogene Proteins c-hck

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Chicago

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NLM

Edwards, D. P., Wardell, S. E., & Boonyaratanakornkit, V. (2002). Progesterone receptor interacting coregulatory proteins and cross talk with cell signaling pathways. In J Steroid Biochem Mol Biol (Vol. 83, pp. 173–186). England. https://doi.org/10.1016/s0960-0760(02)00265-0

Edwards, Dean P., Suzanne E. Wardell, and Viroj Boonyaratanakornkit. “Progesterone receptor interacting coregulatory proteins and cross talk with cell signaling pathways.” In J Steroid Biochem Mol Biol, 83:173–86, 2002. https://doi.org/10.1016/s0960-0760(02)00265-0.

Edwards DP, Wardell SE, Boonyaratanakornkit V. Progesterone receptor interacting coregulatory proteins and cross talk with cell signaling pathways. In: J Steroid Biochem Mol Biol. 2002. p. 173–86.

Edwards, Dean P., et al. “Progesterone receptor interacting coregulatory proteins and cross talk with cell signaling pathways.” J Steroid Biochem Mol Biol, vol. 83, no. 1–5, 2002, pp. 173–86. Pubmed, doi:10.1016/s0960-0760(02)00265-0.

Edwards DP, Wardell SE, Boonyaratanakornkit V. Progesterone receptor interacting coregulatory proteins and cross talk with cell signaling pathways. J Steroid Biochem Mol Biol. 2002. p. 173–186.