Title

Characterization of a novel and specific inhibitor for the pro-apoptotic protease Omi/HtrA2

Authors

Authors

L. Cilenti; Y. Lee; S. Hess; S. Srinivasula; K. M. Park; D. Junqueira; H. Davis; J. V. Bonventre; E. S. Alnemri;A. S. Zervos

Comments

Authors: contact us about adding a copy of your work at STARS@ucf.edu

Abbreviated Journal Title

J. Biol. Chem.

Keywords

PROGRAMMED CELL-DEATH; SERINE-PROTEASE; PROTEINS; DROSOPHILA; HTRA2; GENE; XIAP; IDENTIFICATION; MITOCHONDRIA; INTERACTS; Biochemistry & Molecular Biology

Abstract

Omi/HtrA2 is a mammalian serine protease with high homology to bacterial HtrA chaperones. Omi/HtrA2 is localized in mitochondria and is released to the cytoplasm in response to apoptotic stimuli. Omi/HtrA2 induces cell death in a caspase-dependent manner by interacting with the inhibitor of apoptosis protein as well as in a caspase-independent manner that relies on its protease activity. We describe the identification and characterization of a novel compound as a specific inhibitor of the proteolytic activity of Omi/HtrA2. This compound (ucf-101) was isolated in a high throughput screening of a combinatorial library using bacterially made Omi-(134-458) protease and fluorescein-casein as a generic substrate. ucf-101 showed specific activity against Omi/HtrA2 and very little activity against various other serine proteases. This compound has a natural fluorescence that was used to monitor its ability to enter mammalian cells. ucf-101, when tested in caspase-9 (-/-) null fibroblasts, was found to inhibit Omi/HtrA2-induced cell death.

Journal Title

Journal of Biological Chemistry

Volume

284

Issue/Number

13

Publication Date

1-1-2003

Document Type

Article

Language

English

First Page

11489

Last Page

11494

WOS Identifier

WOS:000181425900043

ISSN

0021-9258

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