Phosphorylation of CtBP1 by cAMP-dependent protein kinase modulates induction of CYP17 by stimulating partnering of CtBP1 and 2

The Journal of Biological Chemistry
Eric Dammer, Marion B Sewer

Abstract

In the human adrenal cortex, the peptide hormone adrenocorticotropin (ACTH) directs cortisol and adrenal androgen biosynthesis by activating a cAMP/cAMP-dependent protein kinase (PKA) pathway. Carboxyl-terminal binding protein 1 (CtBP1) is a corepressor that regulates transcription of the CYP17 gene by periodically interacting with steroidogenic factor-1 in response to ACTH signaling. Given that CtBP1 function is regulated by NADH binding, we hypothesized that ACTH-stimulated changes in cellular pyridine nucleotide concentrations modulate the ability of CtBP1 to repress CYP17 transcription. Further, we postulated that PKA evokes changes in the phosphorylation status of CtBP1 that control the ability of the protein to bind to steroidogenic factor-1 and the coactivator GCN5 (general control nonderepressed 5) and repress CYP17 gene expression. We show that ACTH alters pyridine nucleotide redox state and identify amino acid residues in CtBP1 that are targeted by PKA and PAK6. Both ACTH/cAMP signaling and NADH/NAD+ ratio stimulate nuclear-cytoplasmic oscillation of both CtBP proteins. We provide evidence that PKA 1) induces metabolic changes in the adrenal cortex and 2) phosphorylates CtBP proteins, particularly CtBP1 at T144, resul...Continue Reading

References

Feb 1, 1976·Biulleten' eksperimental'noĭ biologii i meditsiny·Iu P ShorinG S Iakobson
Jan 1, 1991·Hormone Research·M J SaadS T Saad
Oct 11, 1994·Proceedings of the National Academy of Sciences of the United States of America·V CavaillèsM G Parker
Feb 1, 1994·Molecular and Cellular Endocrinology·K G MountjoyR D Cone
Feb 16, 2002·Science·Qinghong ZhangRichard H Goodman
Oct 22, 2002·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Hershel RaffEric P Widmaier
Nov 7, 2002·Molecular Cell·Vivek KumarAneel K Aggarwal
May 30, 2003·Molecular and Cellular Biology·Hiroshi TazawaJohanna Zilliacus
Jun 5, 2003·Molecular and Cellular Endocrinology·Gunnar MellgrenJohan Lund
Jul 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Clark C FjeldRichard H Goodman
Jul 23, 2003·Nature Structural Biology·Christopher J BarnesRakesh Kumar
Jan 23, 2004·The Journal of Biological Chemistry·Mark ChristianMalcolm G Parker
Apr 3, 2004·Nucleic Acids Research·Audrey CastetVincent Cavaillès
Apr 19, 2005·Nature Structural & Molecular Biology·Jae-Hwan KimHong-Duk Youn
Dec 17, 2005·The Journal of Biological Chemistry·Ling-Jun ZhaoG Chinnadurai
Jan 24, 2006·Molecular and Cellular Biology·Laurent BartholinDavid Wotton
Jun 3, 2006·Proceedings of the National Academy of Sciences of the United States of America·Qinghong ZhangRichard H Goodman
Jun 20, 2006·Molecular and Cellular Biology·Alexis VergerMerlin Crossley
Jul 21, 2006·Pathophysiology of Haemostasis and Thrombosis·Bruce Furie, Barbara C Furie
Nov 7, 2006·Nucleic Acids Research·Jorge Lopez-GarciaSimak Ali
Dec 13, 2006·Biochemical and Biophysical Research Communications·Younes AchouriEmile Van Schaftingen
Jan 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·Qinghong ZhangRichard H Goodman
May 30, 2007·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Wilma M FrederiksCornelis J F Van Noorden
Jun 19, 2007·Biochimica Et Biophysica Acta·Kate G R QuinlanMerlin Crossley

❮ Previous
Next ❯

Citations

Sep 3, 2013·Histochemistry and Cell Biology·Carmen ValenteDaniela Corda
Aug 22, 2008·Biology of Reproduction·Stephanie D FiedlerLane K Christenson
Jun 18, 2010·Biology of Reproduction·Jon D Hennebold
May 17, 2008·Genes & Development·Shingo KajimuraBruce M Spiegelman
Oct 6, 2012·The Journal of Endocrinology·F X DonadeuS D Sontakke
Sep 16, 2008·Journal of Animal Science·M Z Carletti, L K Christenson
Jun 14, 2013·International Journal of Cell Biology·Jung S Byun, Kevin Gardner
Aug 4, 2009·Trends in Endocrinology and Metabolism : TEM·Lacey J LuenseLane K Christenson
Jan 13, 2011·The EMBO Journal·Takuya ShirakiharaMasao Saitoh
Jan 15, 2010·The Biochemical Journal·Claire M Wells, Gareth E Jones
Oct 16, 2014·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Zhenyu WangShaoguo Ru
Feb 14, 2018·Molecular Medicine Reports·Piotr CelichowskiMarcin Ruciński

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Related Papers

Cell Cycle
Ling-Zun Zhao, G Chinnadurai
Reproduction : the Official Journal of the Society for the Study of Fertility
Takuya MishimaToshihiro Takizawa
Biology of Reproduction
Youngsok ChoiAleksandar Rajkovic
© 2021 Meta ULC. All rights reserved