3 votes

Kinase independent inhibition of NFκB transcriptional activity by GRK5 through IκBα stabilization.

Daniela Sorriento¹, Michele Ciccarelli¹, Gaetano Santulli¹, Alfonso Campanile¹, Giovanna Giuseppina Altobelli², Vincenzo Cimini², Gennaro Galasso¹, Dalila Astone³, Federico Piscione², Lucio Pastore³, Bruno Trimarco² & Guido Iaccarino²

Correspondence: (Login to view email address)

1. Dipartimento di Medicina Clinica, Scienze Cardiovascolari ed Immunologiche, Università Federico II, Napoli, Italy
2. Dipartimento di Scienze Biomorfologiche e Funzionali, Federico II University, Napoli, Italy
3. CEINGE- -Biotecnologie Avanzate, Napoli, Italy

PDF (442.7 KB)

Document Type:

Manuscript

Date:

Received 29 September 2007 07:20 UTC; Posted 01 October 2007

Subjects:

Immunology, Molecular Cell Biology

Tags:

• cell signalling
• Signal transduction
• transcription

Abstract:

Members of the G protein receptor kinase (GRK) family that regulates receptor desensitization and members of the nuclear transcription factors family NFκB have been recently and convincingly demonstrated to interact, although the effects on transcription and gene expression have not yet been described. Using overexpression, knockdown (small interfering RNA) and mutagenesis experiments, we demonstrate that GRK5 couples to and stabilizes the NFκB inhibitor IκBα, and inhibits NFκB activity. Studies with minigenes suggest that the N-terminal Regulation of G protein Signaling (RGS) homology (RH) domain confers GRK5 such ability. GRK5-RH domain overexpression affects NFκB dependent phenotypes, such as apoptosis protection, cytokine production and inflammation and tissue regeneration. Our results reveal a novel, unexpected role of GRK5 in NFκB transcription activity regulation that represents a possible target for diagnostic and therapeutics.

Discussion

Votes:

3 votes

(Login to vote)

Comments:

0 comments

(Login to post a comment)

Share:

(Login to share with a colleague)

Additional information

License:

This document is licensed to the public under the Creative Commons Attribution 2.5 License

How to cite this document:

Sorriento, Daniela , Ciccarelli, Michele , Santulli, Gaetano , Campanile, Alfonso , Altobelli, Giovanna Giuseppina , Cimini, Vincenzo , Galasso, Gennaro, Astone, Dalila , Piscione, Federico, Pastore, Lucio, Trimarco, Bruno, and Iaccarino, Guido . Kinase independent inhibition of NFκB transcriptional activity by GRK5 through IκBα stabilization.. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2007.1196.1> (2007)

Version info:

Other versions of this document in Nature Precedings

None.

Other versions of this document elsewhere on the web

None known.

Submit a new version link