The serine protease HtrA2/Omi cleaves Parkin and irreversibly inactivates its E3 ubiquitin ligase activity

Hye Min Park, Goo Young Kim, Min Kyung Nam, Geun Hye Seong, Chul Han, Kwang Chul Chung, Seong Man Kang, Hyangshuk Rhim

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The serine protease HtrA2 is important in regulating not only apoptosis but also cellular homeostasis. Recently, several lines of evidence suggest that HtrA2 may be intimately associated with Parkin; however, little is known about the functional relationships between HtrA2 and Parkin. Here we have shown that HtrA2 is co-localized with Parkin in the cytosol through the release of HtrA2 from the mitochondria upon cellular stresses. Moreover, endogenous levels of Parkin were significantly decreased in wild-type (HtrA2+/+) mouse embryonic fibroblasts (MEF) compared with those in HtrA2-knockout (HtrA2-/-) MEF under the same stress conditions. Using cleavage and binding assays, we have demonstrated that HtrA2 specifically binds to and directly cleaves the E3 ubiquitin (Ub) ligase Parkin. Interestingly, the HtrA2-mediated Parkin cleavage irreversibly disrupts Parkin-mediated synphilin-1 ubiquitination and autoubiquitination, indicating that HtrA2 may play a critical role in the Parkin-related pathway involved in the ubiquitin proteasome system.

Original languageEnglish
Pages (from-to)537-542
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume387
Issue number3
DOIs
Publication statusPublished - 2009 Sep 25

Fingerprint

Ubiquitin-Protein Ligases
Serine Proteases
Fibroblasts
Mitochondria
Ubiquitination
Proteasome Endopeptidase Complex
Ubiquitin
Knockout Mice
Cytosol
Assays
Homeostasis
Apoptosis
Omi serine protease

Keywords

  • E3 ubiquitin ligase
  • HtrA2
  • Parkin
  • Serine protease
  • Ubiquitination

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

The serine protease HtrA2/Omi cleaves Parkin and irreversibly inactivates its E3 ubiquitin ligase activity. / Park, Hye Min; Kim, Goo Young; Nam, Min Kyung; Seong, Geun Hye; Han, Chul; Chung, Kwang Chul; Kang, Seong Man; Rhim, Hyangshuk.

In: Biochemical and Biophysical Research Communications, Vol. 387, No. 3, 25.09.2009, p. 537-542.

Research output: Contribution to journalArticle

Park, Hye Min ; Kim, Goo Young ; Nam, Min Kyung ; Seong, Geun Hye ; Han, Chul ; Chung, Kwang Chul ; Kang, Seong Man ; Rhim, Hyangshuk. / The serine protease HtrA2/Omi cleaves Parkin and irreversibly inactivates its E3 ubiquitin ligase activity. In: Biochemical and Biophysical Research Communications. 2009 ; Vol. 387, No. 3. pp. 537-542.
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