Identification of tubulins as substrates of serine protease HtrA1 by mixture-based oriented peptide library screening

Jeremy Chien, Xiaoping He, Viji Shridhar

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Serine protease HtrA1 belongs to a family of chymotrypsin-like proteases that were first identified in bacteria and later in mammalian systems. These proteases were identified as components of protein quality control in prokaryotic systems and as regulators of diverse signaling pathways in mammalian systems. In particular, HtrA1 is implicated in trophoblast cell migration and invasion, tumor progression, chemotherapy-induced cytotoxicity, osteoarthritis, age-related macular degeneration, and pathogenesis of Alzheimer's disease. However, systematic analysis of its potential substrates in biological system is still lacking. Therefore, we performed a mixture-based oriented peptide library screening to identify putative substrates of HtrA1. We identified [AEGR]-[LAGR]-[IAMLR]-[TVIAL] as consensus residues for P1 to P4 sites. We identified several putative substrates of HtrA1 involved in the pathogenesis of various diseases. In this study, we report on the identification of tubulins as potential substrates of HtrA1, and validated tubulins as in vitro and intracellular substrates of HtrA1. These results provide initial insights into substrate identification and functional characterization of HtrA1 in pathogenesis of various diseases.

Original languageEnglish (US)
Pages (from-to)253-263
Number of pages11
JournalJournal of Cellular Biochemistry
Volume107
Issue number2
DOIs
StatePublished - May 15 2009
Externally publishedYes

Keywords

  • HtrA1
  • Peptide library
  • Serine protease
  • Tubulins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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