Originally published In Press as doi:10.1074/jbc.M212688200 on May 21, 2003
J. Biol. Chem., Vol. 278, Issue 32, 30272-30282, August 8, 2003
Mild Heat and Proteotoxic Stress Promote Unique Subcellular Trafficking and Nucleolar Accumulation of RGS6 and Other RGS Proteins
ROLE OF THE RGS DOMAIN IN STRESS-INDUCED TRAFFICKING OF RGS PROTEINS*
Tapan K. Chatterjee and
Rory A. Fisher 
From the
Department of Pharmacology, University of Iowa College of Medicine, Iowa
City, Iowa 52242
RGS proteins comprise a large family of proteins named for their ability to
negatively regulate heterotrimeric G protein
signaling. RGS6 is a member of the R7 subfamily of RGS proteins
possessing DEP (disheveled/Egl-10/pleckstrin) homology and GGL (G protein
-subunit-like) domains in addition to the semiconserved RGS domain. Our
previous study documented unusual complexity in splicing of the human
RGS6 gene, and we demonstrated localization of various RGS6 splice
forms at sites other than the plasma membrane, including the cytoplasm and
nucleus, where G proteins are not localized (Chatterjee, T. K., Liu, Z., and
Fisher, R. A. (2003) J. Biol. Chem. 278, 30261–30271). Here we
provide new evidence that mild heat stress, proteasome-mediated proteotoxic
stress, and HSF1 expression induces dramatic relocalization of RGS6 proteins
from such sites to nucleoli. This response was observed in COS-7 cells
expressing various splice forms of RGS6, was not elicited by other forms of
cellular stress and was observed in cells treated with various protein kinase
inhibitors or co-expressing a dominant-negative kinase inactive SAPK. The RGS
domain of RGS6 was identified as a primary structural module providing support
for its stress-induced nucleolar trafficking and various other RGS proteins or
their isolated RGS domains similarly undergo nucleolar migration in response
to heat or proteotoxic stress or during co-expression of HSF1. The atypical
RGS domains of axin and AKAP10 also underwent stress-induced nucleolar
trafficking while structural domains outside of the RGS domain of some RGS
proteins can override nucleolar trafficking in response to stress. Inhibition
of rDNA transcription also promoted nucleolar migration of RGS6, a response
previously observed in a subset of nucleolar proteins. The DEP domain of RGS6,
but not its RGS domain, conferred structural support for its
transcription-linked nucleolar migration. RGS6 exhibited trafficking from
subnuclear dots to nucleoli in response to heat-, proteotoxic- or
transcription-linked stress. These results provide new evidence that mammalian
RGS proteins undergo unique subcellular trafficking in response to specific
forms of cellular stress and implicate the RGS family of proteins in cellular
stress signaling pathways.
Received for publication, December 12, 2002
, and in revised form, May 16, 2003.
* This work was supported by National Institutes of Health Grants HL41071 and
GM067881 (to R. A. F.) and DK-25295 to the University of Iowa Diabetes and
Endocrinology Research Center. 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.
To whom correspondence should be addressed: University of Iowa College of
Medicine, Dept. of Pharmacology, Iowa City, IA 52242. Tel.: 319-335-8330; Fax:
319-335-8930.
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Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.
