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Pex18p is constitutively degraded during peroxisome biogenesis
1Department of Cell Biology and Anatomy, Mount Sinai School of Medicine, 1190 Fifth Ave., New York, NY 10029-6574, USA. Edward.Purdue@mssm.edu
The Journal of Biological Chemistry
|October 9, 2001
Summary
Yeast peroxins Pex18p and Pex21p are crucial for peroxisome import. Pex18p is rapidly degraded but stabilizes when peroxisomal import is blocked, revealing a novel degradation pathway for organelle biogenesis factors.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Pex18p and Pex21p are related yeast peroxins essential for peroxisome biogenesis.
- They play a redundant role in importing proteins with type 2 peroxisomal targeting sequences (PTS2) via the Pex7p receptor.
Purpose of the Study:
- To investigate the stability and degradation pathway of Pex18p.
- To understand the functional significance of Pex18p turnover in peroxisome biogenesis.
Main Methods:
- Utilized wild-type and various Saccharomyces cerevisiae pex mutants.
- Employed immunoprecipitation to detect protein complexes.
- Analyzed protein ubiquitination and degradation using specific enzyme inhibitors and mutants.
Main Results:
- Pex18p is rapidly degraded in wild-type yeast with a half-life under 10 minutes, likely via proteasomes involving Ubc4p/Ubc5p.
- Pex18p accumulates in pex mutants that block peroxisomal matrix protein import, indicating its turnover is linked to function.
- Pex18p stabilization requires Pex7p and is associated with Pex18p-Pex7p complex formation.
Conclusions:
- Pex18p undergoes rapid, constitutive degradation, a novel finding for an organelle biogenesis factor.
- Pex18p turnover is regulated and linked to its role in peroxisomal protein import.
- Ubiquitination and proteasomal pathways are involved in Pex18p degradation.
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