Molecular determinants of the subcellular localization of the Drosophila Bcl-2 homologues DEBCL and BUFFY.

Full Abstract

The Bcl-2-family of proteins localize to intracellular membranes via a C-terminal hydrophobic membrane anchor (MA) domain, to exert their antiapoptotic or proapoptotic functions. In Drosophila, both Bcl-2 family members, DEBCL and BUFFY, contain an MA. In DEBCL the MA is necessary for the localization of protein to mitochondria and for its proapoptotic activity. BUFFY is highly similar to DEBCL but its localization and function are not clearly defined. Here, we report on comparative analysis of BUFFY and DEBCL to decipher the molecular basis for their subcellular localization. We show that these two proteins localize to distinct intracellular membranes, DEBCL predominantly to mitochondria and BUFFY to endoplasmic reticula (ER). Our results suggest that the MA-flanking residues in DEBCL, homologous to Bcl-X(L), are required for the targeting of DEBCL to mitochondria. The C-terminal positively charged residues present in DEBCL are absent in BUFFY, which allows for its localization to ER. The MA in both proteins is required for the correct targeting and proapoptotic activities of these proteins. Interestingly, a functional nuclear localization signal was identified in the N-terminal region of BUFFY and in the absence of the MA, BUFFY accumulated in the nucleus. The functional implications of these findings are discussed.

Author information

Author/s: Doumanis, J (J); Dorstyn, L (L); Kumar, S (S);

Affiliation: Hanson Institute, IMVS, Frome Road, Adelaide, Australia.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Cell death and differentiation (Cell Death Differ), published in England. (Language: eng)

Reference: 2007-May; vol 14 (issue 5) : pp 907-15

Dates: Created 2007/04/19; Completed 2007/05/23;

PMID: 17205077, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Amino Acid Sequence
Animals
Apoptosis
COS Cells
Cell Nucleus - metabolism
Cercopithecus aethiops
Drosophila Proteins - chemistry; metabolism
Drosophila melanogaster - metabolism
Endoplasmic Reticulum - metabolism
Humans
Membrane Proteins - chemistry; metabolism
Mice

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Buffy protein, Drosophila (0) ; Drosophila Proteins (0) ; Membrane Proteins (0) ; Mutant Proteins (0) ; Nuclear Localization Signals (0) ; Proto-Oncogene Proteins c-bcl-2 (0) ; bcl-X Protein (0) ; debcl protein, Drosophila (0)

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