Evolutionary Conservation Of Bcl2 Family Proteins

Bcl-2, the prototype of the Bcl-2 family proteins, was the first defined molecule involved in apoptosis. It was initially cloned from the t(14;18) breakpoint in human follicular lymphoma (2-4). Although its role as a proto-oncogene was quickly realized, its biological function as an anti-apoptosis gene was not realized until some years later (5,6). A number of proteins were soon discovered that share sequence homology with Bcl-2, but only some of those engage in anti-apoptosis activities; others actually promote apoptosis (see Table 1).

Notably, this family of proteins is evolutionarily conserved. A number of viruses encode Bcl-2 homologs, including most, if not all, gamma herpes viruses (7). Most of these viral homologs are anti-apoptotic, probably because viruses need to keep the infected cells alive for latent and persistent infection (7,8). The nematode Caenorhabditis elegans has its own sequence and functional homologs for a death antagonist, CED-9 (9), and a BH3-only death agonist, EGL-1 (10). On the other hand, only prodeath homologs (dBorg-1/Drob-1/Debcl and dBorg-2/Buffy) have been described in the Drosophila (11). These homologs are discussed in details in Chapters 9 and 10, respectively.

From: Essentials of Apoptosis: A Guide for Basic and Clinical Research Edited by: X-M. Yin and Z. Dong © Humana Press Inc., Totowa, NJ

Table 1

The Bcl-2 Family Proteins

Function Organisms Members BH domainsa

Table 1

The Bcl-2 Family Proteins

Function Organisms Members BH domainsa

C. elegans Virus

Xenopus

Bcl-2, Bcl-XL, Bcl-W, Mcl-1, A1/Bfl-1, Boo/Diva, Bcl-B/Bcl-2L-10/Nrh CED-9

E1B-19K (Adenovirus), BHRF-1(EBV), KS-Bcl-2 (HHV8), ORF16 (HSV), LMW5-HL (ASFV) XR1, XR11

Multidomain

Pro-apoptosis

Mammals

Bax, Bak, Bok/Mtd, Bcl-xS, Bcl-GL Bad, Bid, Bik/Nbk, Blk, Hrk/DP5, Bim/Bod, Bmf, Nip3/BNIP3, Nix/Bnip3L, Noxa/APR, PUMA, MAP-1, Bcl-GS

Multidomain BH3-only

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