Bcl-2 Mutants with Restricted Subcellular Location Reveal Spatially Distinct Pathways for Apoptosis in Different Cell Types

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1996 Aug 15

PMID 8861942

Citations 103

Authors

W Zhu

A Cowie

G W Wasfy

L Z Penn

B Leber

D W Andrews

Affiliations

Soon will be listed here.

Abstract

Human Bcl-2 is located in multiple intracellular membranes when expressed in MDCK and Rat-1/myc cells. We restricted expression to the endoplasmic reticulum or mitochondria by exchanging the Bcl-2 carboxy-terminal insertion sequence for an equivalent sequence from cytochrome b5 or ActA, respectively. MDCK cells are protected from serum deprivation-induced apoptosis by both wild-type Bcl-2 and the mutant targeted to mitochondria but not by the mutant targeted to endoplasmic reticulum. In contrast, when expressed in Rat-1/myc cells, the Bcl-2 mutant located at the endoplasmic reticulum is more effective than that targeted to mitochondria. In MDCK cells both mutants bind Bax as effectively as wild-type, demonstrating that Bax binding is not sufficient to prevent apoptosis.

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