Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2010 Mar;151(3):855-8.
doi: 10.1210/en.2009-1503.

TORC: a new twist on corticotropin-releasing hormone gene expression

Robert L Spencer  1 , Michael J Weiser
Affiliations
Comment

TORC: a new twist on corticotropin-releasing hormone gene expression

Robert L Spencer et al. Endocrinology. 2010 Mar.
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
Schematic representation of TORC signaling. The activity of TORC is dependent on its phosphorylation state. Unlike most transcriptional coactivators, TORC is sequestered in the cytoplasm by the scaffolding protein 14-3-3 when in the phosphorylated state and is thereby rendered inactive. Upon dephosphorylation, the tetrameric TORC complex accumulates in the nucleus where it interacts with the dimerization and DNA binding domain of CREB and facilitates the recruitment of the preinitiation complex (including TAFII130), thereby potentiating transcriptional activation of CREB-dependent genes (such as the CRH gene). The phosphorylation state of TORC is controlled by the opposing effects of the calcium-sensitive phosphatase calcineurin (Cn), and the AMP kinase family of serine/threonine kinases (AMPK, SIK, MARK). In excitable cells, an increase in intracellular calcium via voltage-gated calcium channels activates calcineurin resulting in the dephosphorylation and nuclear translocation of TORC. Additionally, stimulation of adenylate cyclase (AC) via G protein-coupled receptors, or by forskolin, results in activation of PKA, which in turn inhibits members of the AMPK family such as SIK. This prevents TORC sequestration in the cytoplasm, thereby resulting in greater nuclear accumulation of TORC. CBP, CREB binding protein; Ca2+, calcium; CRE, cAMP response element; MARK, microtubule-associated protein affinity-regulating kinase; NT, neurotransmitter; p300, E1A binding protein p300; PIC, preinitiation complex; TAFII130, subunit of transcription factor IID; TATA, conserved DNA promoter sequence 5′-TATAAA-3′; SIK, salt-inducible kinase.
See this image and copyright information in PMC

Comment on

References

    1. Sawchenko PE, Imaki T, Potter E, Kovács K, Imaki J, Vale W 1993 The functional neuroanatomy of corticotropin-releasing factor. Ciba Found Symp 172:5–21; discussion 21–29 - PubMed
    1. Bale TL, Vale WW 2004 CRF and CRF receptors: role in stress responsivity and other behaviors. Annu Rev Pharmacol Toxicol 44:525–557 - PubMed
    1. Owens MJ, Nemeroff CB 1993 The role of corticotropin-releasing factor in the pathophysiology of affective and anxiety disorders: laboratory and clinical studies. Ciba Found Symp 172:296–308; discussion 308–316 - PubMed
    1. Nemeroff CB, Vale WW 2005 The neurobiology of depression: inroads to treatment and new drug discovery. J Clin Psychiatry 66(Suppl 7):5–13 - PubMed
    1. Herman JP, Schafer MK, Thompson RC, Watson SJ 1992 Rapid regulation of corticotropin-releasing hormone gene transcription in vivo. Mol Endocrinol 6:1061–1069 - PubMed

Publication types

MeSH terms