Expression of a murine homologue of the inhibitor of apoptosis protein is related to cell proliferation

Expression of a murine homologue of the inhibitor of apoptosis protein is related to cell proliferation

Department of Developmental Genetics, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan

Communicated by Stanley J. Korsmeyer, Dana–Farber Cancer Institute, Boston, MA (received for review May 13, 1998)

Abstract

The inhibitor of apoptosis (IAP) proteins form a highly conserved gene family that prevents cell death in response to a variety of stimuli. Herein we describe a newly defined murine IAP, designated Tiap, that proved to be a murine homologue of human survivin based on sequence comparison. TIAP has one baculovirus IAP repeat and lacks a C-terminal RING finger motif. TIAP interacted with the processed form of caspase 3 and inhibited caspase-induced cell death. Histological examinations revealed that TIAP is expressed in growing tissues such as thymus, testis, and intestine of adult mice and many tissues of embryos. In in vitro studies, TIAP was induced in splenic T cells activated with anti-CD3 antibody or Con A, and the expression of TIAP was up-regulated in synchronized NIH 3T3 cells at S to G₂/M phase of the cell cycle. We propose that during cell proliferation, cellular protective activity may be augmented with inducible IAPs such as TIAP.

Footnotes

↵ * Present address: Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.
↵ † To whom reprint requests should be addressed. e-mail: tokuhisa{at}med.m.chiba-u.ac.jp.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AB013819 for Tiap).
ABBREVIATIONS:

IAP, inhibitor of apoptosis,

BIR, baculovirus IAP repeat;

GST,

glutathione S-transferase;

TNF,

tumor necrosis factor;

EST,

expressed sequence tag