Skip to main content

S-nitrosylation of heterogeneous nuclear ribonucleoprotein A/B regulates osteopontin transcription in endotoxin-stimulated murine macrophages.

Publication ,  Journal Article
Gao, C; Guo, H; Wei, J; Mi, Z; Wai, P; Kuo, PC
Published in: J Biol Chem
March 19, 2004

Osteopontin (OPN) is a highly hydrophilic and negatively charged sialoprotein of approximately 298 amino acids that contains a Gly-Arg-Gly-Asp-Ser sequence. It is a secreted protein with diverse regulatory functions, including cell adhesion and migration, tumor growth and metastasis, atherosclerosis, aortic valve calcification, and repair of myocardial injury. Despite the many recognized functions of OPN, very little is known of the transcriptional regulation of OPN. In this regard, we have previously demonstrated that OPN transcription and promoter activity are significantly up-regulated in response to NO in a system of endotoxin-stimulated murine macrophages. However, the specific cis- and trans-regulatory elements that determine the extent of endotoxin- and NO-mediated induction of OPN synthesis are unknown. In this follow-up study, we demonstrate that: 1) OPN gene transcription is regulated by a constitutive transcriptional repressor protein, heterogeneous nuclear ribonucleoprotein A/B (hnRNP A/B); 2) inhibition of in vivo hnRNP DNA binding activity is accompanied by increased S-nitrosylation of hnRNP A/B in the setting of lipopolysaccharide (LPS)-mediated NO synthesis; 3) inhibition of LPS mediated NO synthesis restores hnRNP DNA binding and decreases the extent of S-nitrosylation; and 4) S-nitrosylation of hnRNP at cysteine 104 inhibits in vitro DNA binding activity, which is reversed by dithiothreitol. Our findings suggest that LPS induced S-nitrosylation of hnRNP inhibits its activity as a constitutive repressor of the OPN promoter and results in enhanced OPN expression.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

March 19, 2004

Volume

279

Issue

12

Start / End Page

11236 / 11243

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Sialoglycoproteins
  • Sequence Deletion
  • Promoter Regions, Genetic
  • Osteopontin
  • Nitroso Compounds
  • Mice
  • Macrophages
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • Gene Expression Regulation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gao, C., Guo, H., Wei, J., Mi, Z., Wai, P., & Kuo, P. C. (2004). S-nitrosylation of heterogeneous nuclear ribonucleoprotein A/B regulates osteopontin transcription in endotoxin-stimulated murine macrophages. J Biol Chem, 279(12), 11236–11243. https://doi.org/10.1074/jbc.M313385200
Gao, Chengjiang, Hongtao Guo, Junping Wei, Zhiyong Mi, Philip Wai, and Paul C. Kuo. “S-nitrosylation of heterogeneous nuclear ribonucleoprotein A/B regulates osteopontin transcription in endotoxin-stimulated murine macrophages.J Biol Chem 279, no. 12 (March 19, 2004): 11236–43. https://doi.org/10.1074/jbc.M313385200.
Gao, Chengjiang, et al. “S-nitrosylation of heterogeneous nuclear ribonucleoprotein A/B regulates osteopontin transcription in endotoxin-stimulated murine macrophages.J Biol Chem, vol. 279, no. 12, Mar. 2004, pp. 11236–43. Pubmed, doi:10.1074/jbc.M313385200.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

March 19, 2004

Volume

279

Issue

12

Start / End Page

11236 / 11243

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Sialoglycoproteins
  • Sequence Deletion
  • Promoter Regions, Genetic
  • Osteopontin
  • Nitroso Compounds
  • Mice
  • Macrophages
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • Gene Expression Regulation