Conclusion

Protein

B-Cell lymphoma 2 is a protein that is encoded in humans, The Bcl-2 protein is a regulatory protein that regulates apoptosis, cell death. Bcl-2 is also able to regulate calcium homeostasis, neuronal activity , autophagy, and mitochondria dynamics and energetics (2,20,21). The Bcl-2 protein has been found to be localized in (8,9) Outer Mitochondrial Membrane, Smooth Endoplasmic Reticulum Membrane, Nuclear Envelope. Bcl-2 is able to be pro-apoptotic of anti-apoptotic depending on the family from which it is found (8,9).

Gene

Bcl-2 is a 203,035 bp long gene with 4 transcript variant possibilities. Among these 4 transcript variants possibilities with two isoforms being protein coding, Isoform Alpha and Isoform Beta. The Beta transcript variant is a result of the differentiation in the 3' UTR and coding region compared to the alpha variant alpha resulting in a shorter isoform. Due to its shortened polypeptide only totaling 205aa, the Beta isoform seems to be less of an active anti-apoptotic protein than the Alpha isoform. This occurs from it's loss of the BH2 (187-202aa) domain as well the transmembrane domain found in isoform Alpha at 212aa-233aa(7). The Alpha isoform exerts its effects as an anti-apoptotic protein by inhibiting pro-apoptotic Bcl-2 family proteins(15). When mutations occur that effect expression, throwing off the balance of anti- and pro-apoptotic proteins to favor anti-apoptotic ones such as Bcl-2, cell death signaling is disrupted and uncontrolled cell proliferation can occur leading to multiple forms of cancer(16).

Associated Diseases

When BCl-2 undergoes mutation, damage, underexpression or overexpression within a cell cancers are usually formed. Some of these diseases include, Thrombocytopenia with absent radius (TAR), Severe congenital neutropenia (SCN), Renal cell carcinomas (RCC) ,Dyskeratosis congenita (DC), and Lymphoma (37). These can be minimized or cured in some cases with the use of inhibitory Bcl-2 drugs such as Venetoxlax, the first FDA approved Bcl-2 inhibitor (41,42).