OBJECTIVE Bcl-xL is an antiapoptotic member of the Bcl-2 family of proteins and a potent regulator of cell death. We investigated the importance of Bcl-xL for beta-cells by deleting the Bcl-x gene specifically in beta-cells and analyzing their survival in vivo and in culture. RESEARCH DESIGN AND METHODS Islets with beta-cells lacking the Bcl-x gene were assessed in vivo by histology and by tr...

Bcl-2 family proteins are key regulators of apoptosis and function as cell death antagonists (e.g., Bcl-2, Bcl-XL, and Mcl-1) or agonists (e.g., Bax, Bad, and Bak). Here we report that among the Bcl-2 family of proteins tested (Bcl-2, Bcl-XL, Mcl-1, Bax, Bad, and Bak), Bcl-XL was unique in that its protein levels were tightly regulated by hemopoietins in both immortal and primary myeloid progen...

UNLABELLED KRAS mutations are frequently detected in human colorectal cancer and contribute to de novo apoptosis resistance and ultimately therapeutic failure. To overcome KRAS-mediated apoptosis resistance, the irreversible proteasome inhibitor, carfilzomib, was evaluated and found to potently induce Noxa, which was dependent upon c-Myc, and Bik. Isogenic mutant versus wild-type KRAS carcinoma...

OBJECTIVES To explore the roles of Bcl-xl and Bcl-xs in the development and progression of endometrial carcinoma, and to analyze the correlation between Bcl-xl and Bcl-xs. METHODS RT-PCR and Western-blot assay were applied to detect the expressions of Bcl-xl and Bcl-xs in endometrial tissues of various histomorphologic types. RESULTS The Bcl-xl expression levels of simple and atypical hyper...

Treatment of M1 myeloid leukemic cells with interleukin 6 (IL-6) or dexamethasone (DEX), both of which induce differentiation in these cells, down-regulated expression of the apoptosis-suppressing gene bcl-2 and the apoptosis-promoting gene bax but up-regulated expression of the apoptosis-suppressing gene bcl-XL. There was a higher expression of bcl-XL in cells treated with DEX or DEX plus IL-6...

The Bcl-2 related protein Bad is a promoter of apoptosis and has been shown to dimerize with the anti-apoptotic proteins Bcl-2 and Bcl-XL. Overexpression of Bad in murine FL5.12 cells demonstrated that the protein not only could abrogate the protective capacity of coexpressed Bcl-XL but could accelerate the apoptotic response to a death signal when it was expressed in the absence of exogenous B...

Bcl-xL suppresses mitochondria-mediated apoptosis and is frequently overexpressed in cancer to promote cancer cell survival. Bcl-xL also promotes metastasis. However, it is unclear whether this metastatic function is dependent on its anti-apoptotic activity in the mitochondria. Here we demonstrate that Bcl-xL promotes metastasis independent of its anti-apoptotic activity. We show that apoptosis...

Maturation of neuronal synapses is thought to involve mitochondria. Bcl-xL protein inhibits mitochondria-mediated apoptosis but may have other functions in healthy adult neurons in which Bcl-xL is abundant. Here, we report that overexpression of Bcl-xL postsynaptically increases frequency and amplitude of spontaneous miniature synaptic currents in rat hippocampal neurons in culture. Bcl-xL, ove...

Bcl-xL is a member of the Bcl-2 family, playing a critical role in the survival of tumor cells. Here, we show that Bcl-xL oncogenic function can be uncoupled from its anti-apoptotic activity when it is regulated by the post-translational deamidation of its Asn52.Bcl-xL activity can be regulated by post-translational modifications: deamidation of Asn52 and 66 into Asp residues was reported to oc...

Cellular and molecular characterization of osteoclasts (OCL) has been extremely difficult since OCL are rare cells, and are difficult to isolate in large numbers. We used the tartrate-resistant acid phosphatase promoter to target the bcl-XL and/or Simian Virus 40 large T antigen (Tag) genes to cells in the OCL lineage in transgenic mice as a means of immortalizing OCL precursors. Immunocytochem...