BCL‐XL binds and antagonizes RASSF6 tumor suppressor to suppress p53 expression

Abstract

RASSF6, a member of the tumor suppressor Ras-association domain family proteins, induces apoptosis in the caspase-dependent and caspase-independent manners. RASSF6 interacts with MDM2 and stabilizes p53. BCL-XL is a prosurvival member of BCL-2 family proteins. BCL-XL directly inhibits proapoptotic BAX and BAK. BCL-XL also traps tBID, a proapoptotic activator BH3-only protein, and sequesters p53. In addition, BCL-XL regulates the mitochondrial membrane permeability via voltage-dependent anion channel. In these manners, BCL-XL plays an antiapoptotic role. We report the interaction of BCL-XL with RASSF6. BCL-XL inhibits the interaction between RASSF6 and MDM2 and suppresses p53 expression. Consequently, BCL-XL antagonizes RASSF6-mediated apoptosis. Thus, the inhibition of RASSF6-mediated apoptosis also underlies the prosurvival role of BCL-XL.

Mitochondrial Dynamics of Bcl-2 Family Proteins during 17-β-Estradiol-Induced Apoptosis Correlate with the Malignancy of Endometrial Cancer Cells

“…Generally, Bcl-X L is known to play an important antiapoptosis role, and the increase in Bcl-X L expression on the outer mitochondrial membrane indicates an inhibition of the disturbance of the mitochondrial membrane potential. According to a previous report, coexpression of Bcl-X L and p53 is important for cell survival; thus, Bcl-X L induces the survival of cancer cells by inhibiting the function of p53. , In our RT-PCR analysis, p53 mRNA was found to be expressed in HEC1 cells but not HEC50B cells (Figure S2). The expression of p53 mRNA was not induced by E 2 (50 μM) (Figure S2).…”

“…According to a previous report, coexpression of Bcl-X L and p53 is important for cell survival; thus, Bcl-X L induces the survival of cancer cells by inhibiting the function of p53. 33,34 In our RT-PCR analysis, p53 mRNA was found to be expressed in HEC1 cells but not HEC50B cells (Figure S2). The expression of p53 mRNA was not induced by E 2 (50 μM) (Figure S2).…”

The Role of Bcl-xL Protein in Viral Infections

“…In the cytosol, cytochrome c binds apoptotic protease activating factor-1 (Apaf-1) to form an apoptosome, a complex responsible for the initiation of the caspase cascade via caspase-9 activation. The anti-apoptotic Bcl-2 family proteins, such as Bcl-xL, can bind Bax and Bak to inactivate them and prevent PTP-independent mitochondrial permeabilization [28][29][30]. Many viruses are able to upregulate or downregulate Bcl-xL to affect the viability of the cell (Figure 1).…”

Mitochondrial Dynamics of Bcl-2 Family During E2-Induced Apoptosis Correlates with the Malignant of Endometrial Cancer Cells

“…Generally, it is well-known that Bcl-XL plays an important role in apoptosis, and the increase of Bcl-XL expression at mitochondria indicates the inhibition of the disturbance of the mitochondrial membrane potential. According to a previously report, co-expression of Bcl-XL and p53 is important for cell survival, thus, Bcl-XL induced the survival of cancer cells by inhibiting the function of p53 [30,31]. In RT-PCR analysis, p53 mRNA was expressed in HEC1 cells but not HEC50B cells (Supplementary Fig.…”