This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ferguson, J. E.
Right arrow Articles by Patterson, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ferguson, J. E., III
Right arrow Articles by Patterson, C.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2007, p. 6407-6419, Vol. 27, No. 18
0270-7306/07/$08.00+0     doi:10.1128/MCB.00511-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

ASB4 Is a Hydroxylation Substrate of FIH and Promotes Vascular Differentiation via an Oxygen-Dependent Mechanism{triangledown} ,{dagger}

James E. Ferguson III,1,2 Yaxu Wu,1 Kevin Smith,1 Peter Charles,1 Kyle Powers,1 Hong Wang,1 and Cam Patterson1,2,3*

Department of Pharmacology,2 Carolina Cardiovascular Biology Center,1 Department of Medicine, University of North Carolina, Chapel Hill, North Carolina3

Received 23 March 2007/ Returned for modification 26 April 2007/ Accepted 9 July 2007

The molecular mechanisms of endothelial differentiation into a functional vascular network are incompletely understood. To identify novel factors in endothelial development, we used a microarray screen with differentiating embryonic stem (ES) cells that identified the gene for ankyrin repeat and SOCS box protein 4 (ASB4) as the most highly differentially expressed gene in the vascular lineage during early differentiation. Like other SOCS box-containing proteins, ASB4 is the substrate recognition molecule of an elongin B/elongin C/cullin/Roc ubiquitin ligase complex that mediates the ubiquitination and degradation of substrate protein(s). High levels of ASB4 expression in the embryonic vasculature coincide with drastic increases in oxygen tension as placental blood flow is initiated. However, as vessels mature and oxygen levels stabilize, ASB4 expression is quickly downregulated, suggesting that ASB4 may function to modulate an endothelium-specific response to increasing oxygen tension. Consistent with the hypothesis that ASB4 function is regulated by oxygen concentration, ASB4 interacts with the factor inhibiting HIF1{alpha} (FIH) and is a substrate for FIH-mediated hydroxylation via an oxygen-dependent mechanism. Additionally, overexpression of ASB4 in ES cells promotes differentiation into the vascular lineage in an oxygen-dependent manner. We postulate that hydroxylation of ASB4 in normoxia promotes binding to and degradation of substrate protein(s) to modulate vascular differentiation.

* Corresponding author. Mailing address: Division of Cardiology and Carolina Cardiovascular Biology Center, 8200 Medical Biomolecular Research Building, Chapel Hill, NC 27599-7126. Phone: (919) 843-6477. Fax: (919) 843-4585. E-mail: cpatters{at}med.unc.edu

{triangledown} Published ahead of print on 16 July 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, September 2007, p. 6407-6419, Vol. 27, No. 18
0270-7306/07/$08.00+0     doi:10.1128/MCB.00511-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sakamoto, T., Seiki, M. (2009). Mint3 Enhances the Activity of Hypoxia-inducible Factor-1 (HIF-1) in Macrophages by Suppressing the Activity of Factor Inhibiting HIF-1. J. Biol. Chem. 284: 30350-30359 [Abstract] [Full Text]  
  • Cockman, M. E., Webb, J. D., Kramer, H. B., Kessler, B. M., Ratcliffe, P. J. (2009). Proteomics-based Identification of Novel Factor Inhibiting Hypoxia-inducible Factor (FIH) Substrates Indicates Widespread Asparaginyl Hydroxylation of Ankyrin Repeat Domain-containing Proteins. Mol. Cell. Proteomics 8: 535-546 [Abstract] [Full Text]  
  • Bex, C., Knauth, K., Dambacher, S., Buchberger, A. (2007). A yeast two-hybrid system reconstituting substrate recognition of the von Hippel-Lindau tumor suppressor protein. Nucleic Acids Res 35: e142-e142 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»