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J. Biol. Chem., Vol. 282, Issue 52, 37640-37649, December 28, 2007

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RBEL1 Is a Novel Gene That Encodes a Nucleocytoplasmic Ras Superfamily GTP-binding Protein and Is Overexpressed in Breast Cancer^*

From the Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, New York 13210

Rab family proteins are generally known as regulators of protein transport and trafficking. A number of Rab proteins have been implicated in cancer development and/or progression. Here we report the identification of a novel Rab-like protein, which we have named RBEL1 (Rab-like protein 1) for its higher similarity to the Rab subfamily members. We have characterized two isoforms of RBEL1 including the predominant RBEL1A and the less abundant RBEL1B that results from alternative splicing. Both isoforms harbor conserved N-terminal guanine trinucleotide phosphate (GTP) binding domains and, accordingly, are capable of binding to GTP. Both isoforms contain variable C termini and exhibit differential subcellular localization patterns. Unlike known Rabs that are mostly cytosolic, RBEL1B predominantly resides in the nucleus, whereas RBEL1A is localized primarily to the cytosol. Interestingly, a point mutation affecting RBEL1B GTP binding also alters the ability of mutant protein to accumulate in the nucleus, suggesting GTP binding potential to be important for RBEL1B nuclear localization. Our results also indicate that RBEL1A is overexpressed in about 67% of primary breast tumors. Thus, RBEL1A and RBEL1B are novel Rab-like proteins that localize in the nucleus and cytosol and may play an important role in breast tumorigenesis.

Received for publication, June 11, 2007 , and in revised form, October 16, 2007.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) EF156752 (RBEL1A) and EF156753 (RBEL1B).

^* This work was supported in part by National Institutes of Health Grants CA113868, DK067271, and DK062136 (to Y. H.) and ES014489 (to M. S. S.). 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1-4 and Table 1.

¹ To whom correspondence and requests for materials and reprints should be addressed: Dept. of Pharmacology, State University of New York, Upstate Medical University, 750 E. Adams St., Syracuse, NY 13210. Tel.: 315-464-8009; Fax: 315-464-9680; E-mail: huangy{at}upstate.edu.

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This article has been cited by other articles:

				J. Montalbano, K. Lui, M. S. Sheikh, and Y. Huang Identification and Characterization of RBEL1 Subfamily of GTPases in the Ras Superfamily Involved in Cell Growth Regulation J. Biol. Chem., July 3, 2009; 284(27): 18129 - 18142. [Abstract] [Full Text] [PDF]