S-nitrosation of Cys-800 of HIF-1alpha protein activates its interaction with p300 and stimulates its transcriptional activity.

Yasinksa, I.M. and Sumbayev, V. (2003) S-nitrosation of Cys-800 of HIF-1alpha protein activates its interaction with p300 and stimulates its transcriptional activity. FEBS Letters, 549 (1-3). pp. 105-109. ISSN 0014-5793 . (The full text of this publication is not available from this repository)

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Official URL
http://dx.doi.org/10.1016/S0014-5793(03)00807-X

Abstract

Hypoxia inducible factor 1 (HIF-1) is a heterodimeric transcriptional complex that plays pivotal role in the regulation of cellular utilization of oxygen as well as glucose and is an essential regulator of angiogenesis in solid tumor and ischemic disorders. Recently HIF-1alpha, a subunit of HIF-1 complex, was characterized as a potential target for S-nitrosation, providing no information about the impact of this posttranslational modification on the protein transactivation. Cys-800 of HIF-1alpha protein has reactive SH-group, which is critical for the recruitment of p300 co-activator that is necessary for transcriptional activity of HIF-1 complex. Here we report that S-nitrosation of Cys800 activates HIF-1alpha-p300 interaction and stimulates protein transactivation. We have found that S-nitrosation of the HIF1alpha C-terminal domain by nitric oxide derived from donors and nitric oxide synthase increases protein transcriptional activity. The increase of HIF-1 transcriptional activity was not observed in the case of Cys-800 substitution to Ala, though other protein thiol groups were nitrosated. Experiments with GST pull-down assay suggest that S-nitrosation of Cys-800 stimulates the recruitment of p300 co-activator protein to the HIF-1alpha C-terminal domain. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

Item Type: Article
Subjects: Q Science
Divisions: Faculties > University wide - Teaching/Research Groups
Depositing User: Vadim Sumbayev
Date Deposited: 14 Mar 2009 07:44
Last Modified: 14 Jan 2010 14:38
Resource URI: http://kar.kent.ac.uk/id/eprint/9998 (The current URI for this page, for reference purposes)
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