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Originally published In Press as doi:10.1074/jbc.M408163200 on November 1, 2004

J. Biol. Chem., Vol. 280, Issue 1, 805-814, January 7, 2005
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RGS14 Is a Centrosomal and Nuclear Cytoplasmic Shuttling Protein That Traffics to Promyelocytic Leukemia Nuclear Bodies Following Heat Shock*

Hyeseon Cho, Dong-Uk Kim, and John H. Kehrl{ddagger}

From the B-cell Molecular Immunology Section, Laboratory of Immunoregulation, NIAID, National Institutes of Health, Bethesda, Maryland 20892-1876

RGS14, a member of the regulator of G-protein signaling (RGS) protein family, possesses an N-terminal RGS domain, two Raf-like Ras-binding domains, and a GoLoco motif, which has GDP dissociation inhibitor activity. In this study we show that unique among the known mammalian RGS proteins, RGS14 localizes in centrosomes. Its first Ras-binding domain is sufficient to target RGS14 to centrosomes. RGS14 also shuttles between the cytoplasm and nucleus, and its nuclear export depends on the CRM-1 nuclear export receptor. Mutation of a nuclear export signal or treatment with leptomycin B causes nuclear accumulation of RGS14 and its association with promyelocytic leukemia protein nuclear bodies. Furthermore, a point mutant defective in nuclear export fails to target to centrosomes, suggesting that nuclear cytoplasmic shuttling is necessary for its proper localization. Mild heat stress, but not proteotoxic or transcription-linked stresses, re-localizes the RGS14 from the cytoplasm to promyelocytic leukemia nuclear bodies. Expression of RGS14, but not point mutants that disrupt the functional activity of its RGS domain or GoLoco motif, enhances the reporter gene activity. The multifunctional domains and the dynamic subcellular localization of RGS14 implicate it in a diverse set of cellular processes including centrosome and nuclear functions and stress-induced signaling pathways.


Received for publication, July 19, 2004 , and in revised form, October 29, 2004.

* 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.

{ddagger} To whom correspondence should be addressed: Laboratory of Immunoregulation, NIAIDS, National Institutes of Health, Bldg. 10, Rm. 11B08, 10 Center Dr., MSC 1876, Bethesda, MD 20892. Tel.: 301-402-4852; Fax: 301-402-0070; E-mail: jkehrl{at}niaid.nih.gov.


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