Table of Contents
What is the function of Bcl-2?
The BCL-2 family of proteins controls cell death primarily by direct binding interactions that regulate mitochondrial outer membrane permeabilization (MOMP) leading to the irreversible release of intermembrane space proteins, subsequent caspase activation and apoptosis.
What is a Bcl-2 inhibitor?
Targeting BCL2 with the BH3-mimetic, venetoclax. Venetoclax and CLL. Venetoclax and AML. BCL2 inhibition in other hematological malignancies. Lessons from clinical experience with venetoclax to date.
Is Bcl-2 a tumor suppressor?
Apoptosis-Suppressing Oncoprotein Bcl-2 Bcl-2 is widely believed to be an apoptosis suppressor gene. Overexpression of the protein in cancer cells may block or delay onset of apoptosis, by selecting and maintaining long-living cells and arresting cells in the G0 phase of the cell cycle.
Where is Bcl-2 found?
BCL-2 is localized to the outer membrane of mitochondria, where it plays an important role in promoting cellular survival and inhibiting the actions of pro-apoptotic proteins.
What causes Bcl-2 overexpression?
The results suggest that gene amplification and translocation are at least equally common mechanisms causing bcl-2 protein overexpression in DLBCL. Bcl-2 protein overexpression as determined by IHC is associated with poor response to chemotherapy and poor survival.
What do Bcl-2 family proteins have in common?
The Bcl-2 family proteins consists of members that either promote or inhibit apoptosis, and control apoptosis by governing mitochondrial outer membrane permeabilization (MOMP), which is a key step in the intrinsic pathway of apoptosis. A total of 25 genes in the Bcl-2 family were identified by 2008.
How does Bcl-2 prevent apoptosis?
Bcl-2 inhibits apoptosis by increasing the time-to-death and intrinsic cell-to-cell variations in the mitochondrial pathway of cell death. Apoptosis.
What is the result of developing an inhibitor that targets Bcl-2?
Inhibitors of BCL-2, such as venetoclax and navitoclax, were shown to selectively induce apoptosis in malignant cells and have been extensively investigated as single agents and in combination with other drugs in several malignancies, including acute leukemia, lymphomas, and solid tumors.
What causes overexpression of BCL-2?
What chromosome is BCL-2 on?
BCL2 is normally located on chromosome 18q21. 33 in a telomere to centromere orientation. The molecular consequence of the t(14;18) juxtaposes of the BCL2 gene next to IGH locus on the der(14) chromosome, in the same transcriptional orientation as the IGH gene.
Who discovered BCL2?
In 1988, the first demonstration of oncogenic potential of Bcl-2 was made by Reed et al,28 confirming that Bcl-2 is a bona fide protooncogene. Shortly thereafter, the antiapoptotic activity of Bcl-2 was discovered by Vaux et al,11 a milestone in research on Bcl-2 that laid a foundation for the next 2 decades of work.
Does bcl2 exist?
BCL-2 was the first anti-death gene discovered, a milestone with far reaching implications for tumor biology. Experimental therapies targeting Bcl-2-family mRNAs or proteins are currently in clinical testing, raising hopes that a new class of anticancer drugs may soon be available.