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PMID:18182384

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Citation

Hirayama, H, Fujita, M, Yoko-o, T and Jigami, Y (2008) O-mannosylation is required for degradation of the endoplasmic reticulum-associated degradation substrate Gas1*p via the ubiquitin/proteasome pathway in Saccharomyces cerevisiae. J. Biochem. 143:555-67

Abstract

In Saccharomyces cerevisiae, protein O-mannosylation, which is executed by protein O-mannosyltransferases, is essential for a variety of biological processes as well as for conferring solubility to misfolded proteins. To determine if O-mannosylation plays an essential role in endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, we used a model misfolded protein, Gas1*p. The O-mannose content of Gas1*p, which is transferred by protein O-mannosyltransferases, was higher than that of Gas1p. Both Pmt1p and Pmt2p, which do not transfer O-mannose to correctly folded Gas1p, participated in the O-mannosylation of Gas1*p. Furthermore, in a pmt1 Delta pmt2 Delta double-mutant background, degradation of Gas1*p is altered from a primarily proteasome dependent to a vacuolar protease-dependent pathway. This process is in a manner dependent on a Golgi-to-endosome sorting function of the VPS30 complex II. Collectively, our data suggest that O-mannosylation plays an important role for proteasome-dependent degradation of Gas1*p via the ERAD pathway and when O-mannosylation is insufficient, Gas1*p is degraded in the vacuole. Thus, we propose that O-mannosylation by Pmt1p and Pmt2p might be a key step in the targeting of some misfolded proteins for degradation via the proteasome-dependent ERAD pathway.

Links

PubMed Online version:10.1093/jb/mvm249

Keywords

Endoplasmic Reticulum/metabolism; Hydrolysis; Mannose/metabolism; Membrane Glycoproteins/metabolism; Proteasome Endopeptidase Complex/metabolism; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/metabolism; Ubiquitin/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

YEAST:PMT2

involved_in

GO:0071712: ER-associated misfolded protein catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:PMT2

involved_in

GO:0035269: protein O-linked mannosylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:PMT1

involved_in

GO:0071712: ER-associated misfolded protein catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:PMT1

involved_in

GO:0071712: ER-associated misfolded protein catabolic process

ECO:0000316: genetic interaction evidence used in manual assertion

SGD:S000000021

P

Seeded From UniProt

complete

YEAST:PMT1

involved_in

GO:0035269: protein O-linked mannosylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:PMT6

involved_in

GO:0035269: protein O-linked mannosylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:PMT4

involved_in

GO:0035269: protein O-linked mannosylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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