| Description | 25 kDa; 205 amino acids (BCL2b) or 239 amino acids (BCL2a, which has, in addition, a hydrophobic tail for membrane anchorage; this tail seems necessary for anti apoptotic ability); contain homo/heterodimerization domains (BH) and NH domains. |
| Expression | wide; in B and T cells in particular |
| Localisation | mainly in the mitochondrial membrane; other membranes |
| Function | antiapoptosis, through a possibly complex process; dimerization, especially with BAX; role of the BCL2 anti-apoptosis members in forming complexes with caspase-9 and APAF1 (homolog of the nematode CED-4), which prevent them to initiate the protease cascade (through caspase-3 cytochrome C dependent activation and) leading to apoptosis |
| Homology | with Ced9 (nematode C. elegans); with other member of the BCL2 family: 1- apoptosis inhibitors BCLX, MCL1, and 2- apoptosis inducers BAX, BAD, BIK, ... |
| Entity | t(14;18)(q32;q21)/B-cell malignancies --> IgH - BCL2 |
| Disease | B- cell NHL mainly; found in 80 to 90 % of follicular lymphomas, 30% of diffuse large cell lymphomas |
| Prognosis | according to the cyto-pathologic subtype (small cleaved cell follicular lymphomas have a good prognosis; large cell lymphomas have a worse prognosis; the t(14;18) may have no prognostic significance) |
| Cytogenetics | complex karyotypes are frequent with +7, del(6q), +12, + X,... |
| Hybrid/Mutated Gene | 5' BCL2 translocated on chromosome 14 near JH (junctions genes of IgH) and C in 3' |
| Abnormal Protein | no fusion protein, but promoter exchange; the immunoglobulin gene enhancer stimulates the expression of BCL2 |
| Oncogenesis | as BCL2 is an apoptosis inhibitor, cell death is delayed, and there is cell accumulation (more than real transformation) |
| | |
| Entity | chronic lymphocytic leukaemia |
| Oncogenesis | BCL2 is hypomethylated in the promotor region, and, therefore, overexpressed |
| | |
| Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18. |
| Bakhshi A, Jensen JP, Goldman P, Wright JJ, McBride OW, Epstein AL, Korsmeyer SJ |
| Cell. 1985 ; 41 (3) : 899-906. |
| PMID 3924412 |
| |
| Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosome 18. |
| Cleary ML, Sklar J |
| Proceedings of the National Academy of Sciences of the United States of America. 1985 ; 82 (21) : 7439-7443. |
| PMID 2865728 |
| |
| Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. |
| Oltvai ZN, Milliman CL, Korsmeyer SJ |
| Cell. 1993 ; 74 (4) : 609-619. |
| PMID 8358790 |
| |
| Structure, function, and regulation of human cAMP-dependent protein kinases. |
| Taskˆ©n K, Skˆ€lhegg BS, Taskˆ©n KA, Solberg R, Knutsen HK, Levy FO, Sandberg M, Orstavik S, Larsen T, Johansen AK, Vang T, Schrader HP, Reinton NT, Torgersen KM, Hansson V, Jahnsen T |
| Advances in second messenger and phosphoprotein research. 1997 ; 31 : 191-204. |
| PMID 9344252 |
| |
| Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation. |
| Hu Y, Benedict MA, Wu D, Inohara N, Nˆ†ˆ±ez G |
| Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (8) : 4386-4391. |
| PMID 9539746 |
| |
