Subcellular Localization of bcl-2 Protein

Bcl-2 inhibits p53 nuclear import following DNA damage

“…These results are consistent with observations indicating that bcl-2 may selectively alter import of NF-AT (nuclear factor of activated T cells) following T cell activation (Linette et al, 1995;Shibasaki et al, 1997) and, together with cmyc, in¯uence the subcellular distribution of p53 during cell cycle progression in erythroleukemia cells (Ryan et al, 1994). The results of de Jong et al (1994), suggest that the ability of bcl-2 to modulate nuclear import of high molecular weight molecules may be mediated by association with components of the nuclear pore complex. Similarly, recent evidence suggests that alterations in the mitochondrial permeability transition pore may represent an early event involved in the initiation of the cell death program and that bcl-2 may inhibit cell death by preventing the pore transition (Zamzami et al, 1996).…”

“…Therefore, we speculate that this`gatekeeper' function may be an essential component for cell death suppression by bcl-2. Whether the mechanism of the`gatekeeper' involves a physical association of bcl-2 with existing pore complexes within these membrane compartments (de Jong et al, 1994), or is mediated indirectly by competitive interactions with proteins which may be necessary for transmembrane tra cking (Elkind et al, 1995;Naumovski and Cleary, 1996;Shibasaki et al, 1997) or modi®cation of the intracellular ion environment (Greber and Gerace 1995; Marin et al, 1996) remains to be completely elucidated. It is, therefore, conceivable that bcl-2 may function to selectively modulate import events directly at the level of the nuclear pore complex itself or function to modify requisite activation events upstream of membrane translocation.…”

Bcl-2 and Ca2+ homeostasis in the endoplasmic reticulum

“…Interestingly, mitochondrial staining was patchy, reminiscent of mitochondrial contact zones. [5][6][7] This complex distribution (and the putative engagement of Bcl-2 in protein complexes) suggests a pleiotropic effect, with specific and likely different functions in different membrane environments.…”

Bcl-2 differentially targets K-, N-, and H-Ras to mitochondria in IL-2 supplemented or deprived cells: Implications in prevention of apoptosis

“…The protein encoded by the bcl-2 gene is associated with suppression of apoptosis (Miyazaki et al, 1995;Wyllie, 1995;Weller et al, 1995;Go mez et al, 1997). Bcl-2 is located mainly in the outer membrane of mitochondria, as well as in the nuclear envelope and parts of the endoplasmic reticulum (Krajewski et al, 1993;De Jong et al, 1994). Several signal transducing proteins have been reported to interact with Bcl-2, directly or indirectly, including the Ras-related protein p23 R-Ras (Fernandez-Sarabia and Bischo , 1993), H-Ras (Chen and Faller, 1996), the downstream e ector protein kinase Raf-1 (Wang et al, 1996) and the phosphatase calcineurin (Shibasaki et al, 1997).…”