Abstract
In 1988 McCusker and Haber generated a series of mutants which are resistant to the minimum inhibitory concentration of the protein synthesis inhibitor cycloheximide. These cycloheximide-resistant, temperature-sensitive (crl) mutants, in addition, exhibited other pleiotropic phenotypes, e.g., incorrect response to starvation, hypersensitivity against amino acid analogues, and other protein synthesis inhibitors. Temperature sensitivity of one of these mutants, crl3–2, had been found to be suppressed by a mutation, SCL1–1, which resided in an α-type subunit of the 20S proteasome. We cloned the CRL3 gene by complementation and found CRL3 to be identical to theSUG1/CIM3 gene coding for a subunit of the 19S cap complex of the 26S proteasome. Another mutation, crl21, revealed to be allelic with the 20S proteasomal gene PRE3. crl3–2 and crl21 mutant cells show significant defects in proteasome-dependent proteolysis, whereas theSCL1–1 suppressor mutation causes partial restoration of crl3–2-induced proteolytic defects. Notably, cycloheximide resistance was also detected for other proteolytically deficient proteasome mutants (pre1–1,pre2–1, pre3–1, pre4–1). Moreover, proteasomal genes were found within genomic sequences of 9 of 13 chromosomal loci to which crl mutations had been mapped. We therefore assume that most if not all crlmutations reside in the proteasome and that phenotypes found are a result of defective protein degradation.
References
52
Referenced
58
10.1016/0378-1119(89)90113-3
/ Gene by Balzi E. (1989)10.1016/0092-8674(93)90426-Q
/ Cell by Chen P. (1993)10.1146/annurev.bi.65.070196.004101
/ Annu. Rev. Biochem. by Coux O. (1996)10.1128/MCB.15.11.6311
/ Mol. Cell. Biol. by De Marini D.J. (1995)10.1016/S0962-8924(00)89102-3
/ Trends Cell Biol. by Deshaies R. (1995)10.1016/S0021-9258(17)37244-7
/ J. Biol. Chem. by Deveraux Q. (1994)10.1128/MCB.11.1.344
/ Mol. Cell. Biol. by Emori Y. (1991)10.1016/0014-5793(94)80455-9
/ FEBS Lett. by Enenkel C. (1994)10.1016/S0021-9258(17)46265-X
/ J. Biol. Chem. by Fujiwara T. (1990)10.1038/366358a0
/ Nature by Ghislain M. (1993)10.1093/nar/20.6.1425
/ Nucleic Acids Res. by Gietz D. (1992)10.1038/386463a0
/ Nature by Groll M. (1997)10.1083/jcb.75.2.422
/ J. Cell Biol. by Hartwell L.H. (1977)10.1016/S0021-9258(18)53509-2
/ J. Biol. Chem. by Heinemeyer W. (1993)10.1002/j.1460-2075.1991.tb07982.x
/ EMBO J. by Heinemeyer W. (1991)10.1074/jbc.272.40.25200
/ J. Biol. Chem. by Heinemeyer W. (1997)10.1016/S0021-9258(18)53719-4
/ J. Biol. Chem. by Hilt W. (1993)10.1016/S0968-0004(96)10012-8
/ Trends Biochem. Sci. by Hilt W. (1996)10.1016/0092-8674(94)90221-6
/ Cell by Kim Y.J. (1994)10.1126/science.274.5293.1652
/ Science by King R.W. (1996)10.1006/excr.1994.1079
/ Exp. Cell Res. by Kominami K.I. (1994)10.1002/j.1460-2075.1994.tb06948.x
/ EMBO J. by Kornitzer D. (1994)10.1126/science.7725097
/ Science by Löwe J. (1995)10.1101/SQB.1995.060.01.055
/ Cold Spring Harbor Symp. Quant. Biol. by Lupas A. (1995)10.1093/genetics/119.2.303
/ Genetics by McCusker J.H. (1988)10.1093/genetics/119.2.317
/ Genetics by McCusker J.H. (1988)10.1016/0076-6879(91)94060-P
/ Methods Enzymol., by Mortimer R.K. (1991)10.1038/360597a0
/ Nature by Murakami Y. (1992)10.1016/0968-0004(94)90115-5
/ Trends Biochem. Sci. by Peters J.M. (1994)10.1016/0014-5793(92)80438-M
/ FEBS Lett. by Richter-Ruoff B. (1992)10.1016/0014-5793(94)01085-4
/ FEBS Lett. by Richter-Ruoff B. (1994)10.1016/0076-6879(91)94017-7
/ Methods Enzymol., by Rose M.D. (1991)10.1016/0076-6879(91)94022-5
/ Methods Enzymol. by Rothstein R. (1991)10.1038/379655a0
/ Nature by Rubin D.M. (1996)10.1074/jbc.271.51.32810
/ J. Biol. Chem. by Russell S.J. (1996)10.1073/pnas.74.12.5463
/ Proc. Natl. Acad. Sci. USA by Sanger F. (1977)10.1002/yea.320100903
/ Yeast by Schnall R. (1994)10.1016/0014-5793(94)00668-7
/ FEBS Lett. by Schork S.M. (1994)10.1038/369283a0
/ Nature by Schork S.M. (1994)10.1074/jbc.270.44.26446
/ J. Biol. Chem. by Schork S.M. (1995)10.1038/373078a0
/ Nature by Seufert W. (1995)10.1002/j.1460-2075.1990.tb08141.x
/ EMBO J. by Seufert W. (1990)10.1002/j.1460-2075.1992.tb05379.x
/ EMBO J. by Seufert W. (1992){'key': 'B46', 'first-page': '19', 'volume': '194', 'author': 'Sherman F.', 'year': '1991', 'journal-title': 'Methods Enzymol.'}
/ Methods Enzymol. by Sherman F. (1991)10.1016/0014-4827(79)90462-2
/ Exp. Cell Res. by Shilo B. (1979)10.1093/genetics/122.1.19
/ Genetics by Sikorski R.S. (1989)10.1038/357698a0
/ Nature by Swaffield J.C. (1992)10.1038/374088a0
/ Nature by Swaffield J.S. (1995)10.1073/pnas.93.2.856
/ Proc. Natl. Acad. Sci. USA by van Nocker S. (1996)10.1016/0147-619X(86)90051-X
/ Plasmid by Wright A. (1986)10.1128/MCB.15.11.6025
/ Mol. Cell. Biol. by Xu Q. (1995)10.1128/MCB.15.2.731
/ Mol. Cell. Biol. by Yaglom J. (1995)
Dates
Type | When |
---|---|
Created | 12 years, 1 month ago (July 2, 2013, 7:12 p.m.) |
Deposited | 3 years, 5 months ago (Feb. 26, 2022, 9:34 p.m.) |
Indexed | 2 months, 2 weeks ago (June 3, 2025, 12:57 a.m.) |
Issued | 27 years, 8 months ago (Dec. 1, 1997) |
Published | 27 years, 8 months ago (Dec. 1, 1997) |
Published Print | 27 years, 8 months ago (Dec. 1, 1997) |
@article{Gerlinger_1997, title={Yeast Cycloheximide-resistantcrlMutants Are Proteasome Mutants Defective in Protein Degradation}, volume={8}, ISSN={1939-4586}, url={http://dx.doi.org/10.1091/mbc.8.12.2487}, DOI={10.1091/mbc.8.12.2487}, number={12}, journal={Molecular Biology of the Cell}, publisher={American Society for Cell Biology (ASCB)}, author={Gerlinger, Uwe-M. and Gückel, Roland and Hoffmann, Michael and Wolf, Dieter H. and Hilt, Wolfgang}, year={1997}, month=dec, pages={2487–2499} }