Control of proliferation by Bcl-2 family members

Abstract

The anti-proliferative effect of Bcl-2 acts mainly at the level of the G0/G1 phase of the cell cycle. Deletions and point mutations in the bcl-2 gene show that the anti-proliferative activity of Bcl-2, can in some cases, be dissociated from its anti-apoptotic function. This indicates that the effect of Bcl-2 on cell cycle progression can be a direct effect and not only a consequence of its anti-apoptotic activity. Bcl-2 appears to mediate its anti-proliferative effect by acting on both signal transduction pathways (NFAT, ERK) and on specific cell cycle regulators (p27, p130).

Mtd/Bok takes a swing: proapoptotic Mtd/Bok regulates trophoblast cell proliferation during human placental development and in preeclampsia

“…[15][16][17] Data presented herein show that Mtd, a proapoptotic molecule of the Bcl-2 family, is involved in the regulation of both proliferation and cell death in the human placenta in physiological and pathological conditions. In particular, we show that (1) Mtd is expressed in proliferating trophoblast cells during early placental development and in severe early onset PE, where it acts on the G 1 phase of the cell cycle by directly regulating the expression of cyclin E1, (2) Mtd-L is the isoform responsible for this effect on cell proliferation, and (3) Mtd localizes to the nuclear compartment in proliferating cells, whereas during apoptosis it switches localization to the cytoplasm where it interacts with mitochondria.…”

“…[15][16][17] The antiapoptotic members, Bcl-2, BCL-xL, BCL-w, and Mcl-1, have been shown to have inhibitory effects on passage through the cell cycle, whereas the proapoptotic member, Bax, promotes cell proliferation by conferring cell cycle advancement. 17,18,21 Although the Mtd promoter has been found to be activated at the G 1 /S boundary in vitro, 24 we present for the first time direct evidence that the Mtd protein is expressed in cycling cells in vivo.…”

“…[12][13][14] In recent years, it has become apparent that a number of Bcl-2 family members also regulate cell cycle progression. 11,[15][16][17] Interestingly, although antiapoptotic multidomain members slow down progression through the cell cycle, proapoptotic molecules appear to promote cell cycle progression. [15][16][17][18][19][20][21] Matador is a proapoptotic Bcl-2 family member that is highly expressed in reproductive tissues.…”

“…11,[15][16][17] Interestingly, although antiapoptotic multidomain members slow down progression through the cell cycle, proapoptotic molecules appear to promote cell cycle progression. [15][16][17][18][19][20][21] Matador is a proapoptotic Bcl-2 family member that is highly expressed in reproductive tissues. 14,22 Its gene, Mtd, is alternatively spliced and encodes for three protein isoforms Mtd-L, Mtd-S, and Mtd-P, with the L and P isoforms predominating in the human placenta.…”

Apoptosis of HIV-specific CD8+ T cells: an HIV evasion strategy

“…85,132 Bcl-2 is a molecule that mediates both apoptosis and cell-cycle regulation, 159,160 something described also for other Bcl-2 family molecules. 161 We hypothesize that a potential deregulation of Bcl-2-like molecules in HIV-specific CD8 þ T cells could be the linker between a cell-cycle deregulation, activation and apoptosis sensitivity.…”