Bcl-2 blocks or delays apoptosis in many cell systems. The protein exerts its antiapoptotic effect mainly in the membrane of mitochondria. Indeed, emerging evidence supports that the mitochondrion plays an important role in the cell death pathway, integrating different pro- and antiapoptotic stimuli. Since deregulation of the expression of Bcl-2 occurs in a variety of human tumors, modulation of its function is regarded as an exploitable manipulation for pharmacological intervention in antitumor chemotherapy. Phosphorylation of Bcl-2 has been implicated as an important regulatory mechanism of its function and is a common event in response to antimitotic drugs. Recently, a similar post-transcriptional modification was observed in response to DNA-damaging agents in some tumor systems, but this is not a general finding in response to genotoxic drugs. Current investigations indicate that different signaling pathways may be involved in Bcl-2 phosphorylation, likely dependent on the kinases activated by the various stress stimuli. A better understanding of the molecular mechanisms by which Bcl-2 regulates apoptosis could provide insights for a rational design of approaches to enhance the susceptibility to drug-induced cell death.
- Drug response
ASJC Scopus subject areas