Nuclear receptor subfamily 4 group A member 1 (nur77)
HIF

Author: Gianpiero Pescarmona
Date: 31/05/2010

Description

DEFINITION

Nerve Growth factor IB (NGFIB) also known as Nur77 or NR4A1 (nuclear receptor subfamily 4 group A member 1) is a protein that in humans is encoded by the NR4A1 gene.

DatabaseLink
WikigenesURL
GeneCards"URL":

CHEMICAL STRUCTURE AND IMAGES

When relevant for the function

  • Primary structure
  • Secondary structure
  • Tertiary structure
  • Quaternary structure

Model

SYNTHESIS AND TURNOVER

mRNA synthesis

Papers Nur77 promoter

Nur77 activated by hypoxia-inducible factor-1alpha overproduces proopiomelanocortin in von Hippel-Lindau-mutated renal cell carcinoma. 2004

Mutation in the von Hippel-Lindau (VHL) protein associated with renal cell carcinoma causes hypoxia-inducible factor (HIF) to stabilize and consequently to induce various HIF-targeting proteins. In this study, we found that proopiomelanocortin (POMC), an adrenocorticotropic hormone precursor, is up-regulated constitutively in VHL-mutated renal cell carcinoma. A critical transcription factor responsible for POMC overproduction was identified as Nur77, a member of the orphan steroid receptor superfamily. Little is known about how VHL mutation leads to activation of Nur77. We report that Nur77 is directly regulated by HIF. We show that HIF-1alpha, but not HIF-2alpha, binds to a putative HIF responsive element in the Nur77 promoter, activating the expression of Nur77. Mutation or deletion of the HIF binding site in the Nur77 promoter abrogates activation of a luciferase reporter gene under the control of Nur77 promoter by HIF-1alpha. The treatment of Nur77 antisense oligonucleotide reduces POMC transcription under hypoxic conditions. We confirmed that Nur77 and POMC are up-regulated in VHL-mutated renal cell carcinoma. In this study, we provide the first molecular evidence that Nur77 activated by HIF under hypoxic conditions regulates production of the peptide hormone precursor POMC.

Activation of thromboxane A(2) receptors induces orphan nuclear receptor Nurr1 expression and stimulates cell proliferation in human lung cancer cells. 2009

cAMP-induced expression of the orphan nuclear receptor Nur77 in MA-10 Leydig cells involves a CaMKI pathway. 2009

protein synthesis
post-translational modifications
degradation

CELLULAR FUNCTIONS

cellular localization,
biological function

Nur77 Target Proteins

p21 expression is induced by activation of nuclear nerve growth factor-induced Balpha (Nur77) in pancreatic cancer cells. 2009

The orphan nuclear receptor Nur77 suppresses endothelial cell activation through induction of IkappaBalpha expression. 2009

Cotreatment with BCL-2 antagonist sensitizes cutaneous T-cell lymphoma to lethal action of HDAC7-Nur77-based mechanism. 2009

The orphan nuclear receptor NUR77 regulates hormone-induced StAR transcription in Leydig cells through cooperation with Ca2+/calmodulin-dependent protein kinase I. 2008

Nur77 coordinately regulates expression of genes linked to glucose metabolism in skeletal muscle. 2007

Regulation of macrophage inflammatory gene expression by the orphan nuclear receptor Nur77. 2006

Repression

Transcriptional repression of matrix metalloproteinase gene expression by the orphan nuclear receptor NURR1 in cartilage. 2007

  • Structural proteins

REGULATION

DIAGNOSTIC USE

Comments
2010-06-02T23:35:29 - Gianpiero Pescarmona

da finire di controllare

nur77 promoter

Attachments
fileuserdate
nur77_600.gifgp31/05/2010
nur77_966.gifgp31/05/2010
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