The background of BCL2
The Bcl-2 family of apoptosis-related genes plays central roles in regulating apoptotic pathways (reviewed in Thomadaki and Scorilas, 2006). Regulation of cell death through apoptosis is critical for the maintenance of homeostasis, defense against infectious agents, and normal development. Bcl-2 family proteins regulate apoptosis primarily through the regulation of mitochondrial outer membrane permeability. In mammals, the family consists of both prosurvival (antiapoptotic) and proapoptotic (prodeath) members. Cellular homeostasis is thought to be dependent on a balance between the actions of prosurvival and proapoptotic proteins.
Bcl-2 family proteins can be divided into 3 main subfamilies on the basis of their function and the content of their Bcl-2 homology (BH) domains, for example: 1) Prosurvival: Bcl-2, Bcl-XL, Bcl-W, A1, and Mcl-1 2) Proapoptotic (multidomain): Bax, Bak, and Bok. 3) BH3-only (proapoptotic): Bad, Bcl-XS, Bid, Bik, Bim, Blk, Bmf, Bnip, Noxa, and Puma. Prosurvival members inhibit cells from undergoing apoptosis, whereas proapoptotic and BH3-only subfamily members promote apoptosis. There are 4 BH domains (1-4) conserved among Bcl-2 family proteins. The BH domains are important for function as well as for heterodimerization between family members. Typical prosurvival family members have all four BH domains (1-4), whereas proapoptotic (multidomain) members have BH1, 2 and 3 domains and BH3-only members have only the BH3 domain. Overall, the relative ratio of prosurvival and proapoptotic proteins determines the suseptibility of a cell to various apoptotic stimuli. Many Bcl-2 family proteins are differentially expressed in various malignancies and some are useful prognostic biomarkers. Prosurvival proteins are often elevated in diverse cancers and have the potential to confer resistance to both endogenous cell death stimuli and cancer treatments. Alterations in the ratio or levels of Bcl-2 family proteins have been also associated with nonmalignant diseases including neurodegenerative diseases, autoimmune diseases, AIDs, Down’s syndrome, cardiovascular diseases, diabetes, glomerulonephritis, and muscular dystrophy. IMG-5685 recognizes both Bcl-2 alpha and beta isoforms. Human Bcl-2 alpha is a 239 amino acid (aa) protein and human Bcl-2 beta is a 205 aa protein.
Bcl-2 Family Gene Data
| Gene | Species | Gene Symbol | Gene Accession No. | Protein Accession No. |
|---|---|---|---|---|
| Bcl-2 | Human | BCL2 | NM_000633 | P10415 |
| Mouse | Bcl2 | NM_009741 | P10417 | |
| Rat | Bcl2 | NM_016993 | P49950 | |
| Bcl-xL, Bcl-xS | Human | BCL2L1 | NM_138578 | Q07817 |
| Mouse | Bcl2l1 | NM_009743 | Q64373 | |
| Rat | Bcl2l1 | NM_001033672 | P53563 | |
| Bax | Human | BAX | NM_138763 | Q07812 |
| Mouse | Bax | NM_007527 | Q07813 | |
| Rat | Bax | NM_017059 | Q63690 | |
| Bak | Human | BAK1 | NM_001188 | Q16611 |
| Mouse | Bak1 | NM_007523 | O08734 | |
| Rat | Bak1 | NM_053812 | Q9JK59 | |
| Mcl-1 | Human | MCL1 | NM_021960 | Q07820 |
| Mouse | Mcl1 | NM_008562 | P97287 | |
| Rat | Mcl1 | NM_021846 | Q9Z1P3 | |
| Bfl-1/A1 | Human | BCL2A1 | NM_004049 | Q16548 |
| Mouse | Bcl2a1 | NM_009742 | Q07440 | |
| Rat | Bcl2a1 | NM_133416 | Q925A9 | |
| Bcl-w | Human | BCL2L2 | NM_004050 | Q92843 |
| Mouse | Bcl2l2 | NM_007537 | P70345 | |
| Rat | Bcl2l2 | NM_021850 | O88996 | |
| Mtd | Human | BOK | NM_032515 | Q9UMX3 |
| Mouse | Bok | NM_016778 | O35425 | |
| Rat | Bok | NM_017312 | Q792S6 | |
| Diva | Human | BCL2L10 | NM_020396 | Q9HD36 |
| Mouse | Bcl2l10 | NM_013479 | Q9Z0F3 | |
| Rat | Bcl2l10 | NM_053733 | Q99M66 | |
| Bcl-G | Human | BCL2L14 | NM_030766 | Q9BZR8 |
| Mouse | Bcl2l14 | NM_025778 | Q9CPT0 | |
| Bpr | Human | BCL2L12 | NM_052842 | Q9HB09 |
| Mouse | Bcl2l12 | NM_029410 | NP_083686 | |
| Rat | Bcl2l12 | NM_001108480 | NP_001101950 | |
| Hrk | Human | HRK | NM_003806 | O00198 |
| Mouse | Hrk | NM_007545 | P62816 | |
| Rat | Hrk | NM_057130 | P62817 | |
| Bik, Nbk, Blk | Human | BIK | NM_001197 | Q13323 |
| Mouse | Bik | NM_007546 | NP_031572 | |
| Rat | Bik | NM_053704 | Q925D2 | |
| Bid | Human | BID | NM_001196 | P55957 |
| Mouse | Bid | NM_007544 | P70444 | |
| Rat | Bid | NM_022684 | Q9JLT6 | |
| Bad | Human | BAD | NM_032989 | Q92934 |
| Mouse | Bad | NM_007522 | Q61337 | |
| Rat | Bad | NM_022698 | O35147 | |
| Bim | Human | BCL2L11 | NM_006538 | O43521 |
| Mouse | Bcl2l11 | NM_207680 | O54918 | |
| Rat | Bcl2l11 | NM_171988 | O88498 | |
| Puma | Human | BBC3 | NM_014417 | Q9BXH1 |
| Mouse | Bbc3 | NM_133234 | Q99ML1 | |
| Rat | Bbc3 | NM_173837 | Q80ZG6 | |
| Noxa, Apr | Human | PMAIP1 | NM_021127 | Q13794 |
| Mouse | Pmaip1 | NM_021451 | NP_067426 | |
| Rat | Pmaip1 | NM_001008385 | Q5U777 |
Bcl-2 Family Products
Inhibitors
| Cat.No. | Product Name | Activity |
|---|---|---|
| 2160 | Bax channel blocker | Inhibits Bax-mediated mitochondrial cytochrome c release |
| 1786 | Bax inhibitor peptide P5 | Inhibitor of Bax-mediated apoptosis |
| 1785 | Bax inhibitor peptide V5 | Inhibitor of Bax-mediated apoptosis |
| 1787 | Bax inhibitor peptide, negative control | Negative control peptide for Bax inhibitor peptides V5 and P5 (Cat. Nos. 1785 and 1786) |
| 3590 | Gambogic acid | Apoptosis inducer. Inhibits Bcl-2 family proteins |
| 1541 | HA14-1 | Bcl-2 inhibitor. Induces apoptosis |
| 4038 | TW 37 | Bcl-2 inhibitor; induces apoptosis |
Antibodies and Blocking Peptides
| Cat.No. | Product Name | Activity |
|---|---|---|
| 3455 | Anti-Bcl-2 | Antibody recognizing Bcl-2 |
Other
| Cat.No. | Product Name | Activity |
|---|---|---|
| 3367 | AT 101 | Downregulates Bcl-2 and Mcl-1; pro-apoptotic |
| 3526 | BIM, Biotinylated | Bim peptide fragment |
| 2137 | 2,3-DCPE hydrochloride | Downregulates Bcl-XL protein expression |
| 1964 | Gossypol | Pro-apoptotic; downregulates Bcl-2 and Bcl-XL |
| 3816 | Muristerone A | Stimulates Bcl-XL mRNA transcription; antiapoptotic |
| 2907 | SU 9516 | Transcriptionally downregulates Mcl-1; pro-apoptotic |



