HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 7, 4850-4858, February 16, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/7/4850    most recent M610532200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Boswell, S. A. Articles by Lee, S. W. Search for Related Content PubMed PubMed Citation Articles by Boswell, S. A. Articles by Lee, S. W. Social Bookmarking                      What's this?

The Protective Role of a Small GTPase RhoE against UVB-induced DNA Damage in Keratinocytes^*

Sarah A. Boswell¹, Pat P. Ongusaha, Paul Nghiem, and Sam W. Lee²

From the Cutaneous Biology Research Center (CBRC), Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129 and the Dermatology Division, University of Washington, Seattle, Washington 98109

RhoE, a p53 target gene, was identified as a critical factor for the survival of human keratinocytes in response to UVB. The Rho family of GTPases regulates many aspects of cellular behavior through alterations to the actin cytoskeleton, acting as molecular switches cycling between the active, GTP-bound and the inactive, GDP-bound conformations. Unlike typical Rho family proteins, RhoE (also known as Rnd3) is GTPase-deficient and thus expected to be constitutively active. In this study, we investigated the response of cultured human keratinocyte cells to UVB irradiation. RhoE protein levels increase upon exposure to UVB, and ablation of RhoE induction through small interfering RNA resulted in a significant increase in apoptosis and a reduction in the levels of the pro-survival targets p21, Cox-2, and cyclin D1, as well as an increase of reactive oxygen species levels when compared with control cells. These data indicate that RhoE is a pro-survival factor acting upstream of p38, JNK, p21, and cyclin D1. HaCat cells expressing small interfering RNA to p53 indicate that RhoE functions independently of its known associates, p53 and Rho-associated kinase I (ROCK I). Targeted expression of RhoE in epidermis using skin-specific transgenic mouse model resulted in a significant reduction in the number of apoptotic cells following UVB irradiation. Thus, RhoE induction counteracts UVB-induced apoptosis and may serve as a novel target for the prevention of UVB-induced photodamage regardless of p53 status.

Received for publication, November 13, 2006 , and in revised form, December 14, 2006.

^* This work was supported by National Institutes of Health Grants CA80058, CA127247, and CA097216, and Shiseido Research Core funding. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by National Institutes of Health Training Grant AR007098-31.

² To whom correspondence should be addressed: CBRC, Massachusetts General Hospital, Bldg. 149, 13th St., Charlestown, MA 02129. Tel.: 617-726-6691; Fax: 617-643-2334; E-mail: sam.lee{at}cbrc2.mgh.harvard.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H.-H. Lee and Z.-F. Chang Regulation of RhoA-dependent ROCKII activation by Shp2 J. Cell Biol., October 21, 2008; 181(6): 999 - 1012. [Abstract] [Full Text] [PDF]

				A. O. Abu-Yousif, K. A. Smith, S. Getsios, K. J. Green, R. T. Van Dross, and J. C. Pelling Enhancement of UVB-Induced Apoptosis by Apigenin in Human Keratinocytes and Organotypic Keratinocyte Cultures Cancer Res., April 15, 2008; 68(8): 3057 - 3065. [Abstract] [Full Text] [PDF]