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Molecular and Cellular Biology, September 2000, p. 6712-6720, Vol. 20, No. 18
Department of Biochemistry, Hiroshima
University School of Medicine, Minami-ku, Hiroshima 734-8551, Japan
Received 8 February 2000/Returned for modification 20 March
2000/Accepted 9 June 2000
The yeast Saccharomyces cerevisiae has four genes,
MCK1, MDS1 (RIM11),
MRK1, and YOL128c, that encode glycogen
synthase kinase 3 (GSK-3) homologs. The gsk-3 null mutant,
in which these four genes are disrupted, shows temperature sensitivity,
which is suppressed by the expression of mammalian GSK-3
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Yeast Glycogen Synthase Kinase 3 Is Involved in
Protein Degradation in Cooperation with Bul1, Bul2, and Rsp5
and by an
osmotic stabilizer. Suppression of temperature sensitivity by an
osmotic stabilizer is also observed in the bul1 bul2 double
null mutant, and the temperature sensitivity of the bul1
bul2 double null mutant is suppressed by multiple copies of
MCK1. We have screened rog mutants (revertants
of gsk-3) which suppress the temperature sensitivity of the
mck1 mds1 double null mutant and found that two of them, rog1 and rog2, also suppress the temperature
sensitivity of the bul1 bul2 double null mutant. Bul1 and
Bul2 have been reported to bind to Rsp5, a hect (for homologous to
E6-associated-protein carboxyl terminus)-type ubiquitin ligase, but
involvement of Bul1 and Bul2 in protein degradation has not been
demonstrated. We find that Rog1, but not Rog2, is stabilized in the
gsk-3 null and the bul1 bul2 double null
mutants. Rog1 binds directly to Rsp5, and their interaction is
dependent on GSK-3. Furthermore, Rog1 is stabilized in the
npi1 mutant, in which RSP5 expression levels
are reduced. These results suggest that yeast GSK-3 regulates the
stability of Rog1 in cooperation with Bul1, Bul2, and Rsp5.
*
Corresponding author. Mailing address: Department of
Biochemistry, Hiroshima University School of Medicine, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Phone: 81-82-257-5130. Fax: 81-82-257-5134. E-mail:
akikuchi{at}mcai.med.hiroshima-u.ac.jp.
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