colleagues [1] in a recent issue of Arthritis Research & Th erapy. Th ey hypothesized that co-transduction of CD4 + T cells with both forkhead box P3 transcription factor (FoxP3) and Bcl-xL will gener ate highly reactive regulatory T cells (Tregs) that can be used to prevent auto immune disease. Th e authors showed that the accu mulation, persistence, and effi cient function of Tregs were attri...

The heterologous expression of Bax, and other Bcl-2 family members, in the yeast Saccharomyces cerevisiae, has proved to be a valuable reporter system to investigate the molecular mechanisms underlying their interaction with mitochondria. By combining the co-expression of Bax and Bcl-xL mutants with analyzes of their localization and interaction in mitochondria and post-mitochondrial supernatan...

Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis. The role of autophagy and the prognostic value of autophagic genes are largely unknown in HCC. Here, we showed decreased expression of autophagic genes and their corresponding autophagic activity and increased expression of the antiapoptotic gene Bcl-xL in HCC cell lines compared with a normal hepatic cell line. We al...

Multiple myeloma is an incurable malignancy, and there is currently no mouse model that fully recapitulates the development and progression of the disease. We now describe a transgenic mouse that expresses a Bcl-XL transgene under the control of the 3'kappa immunoglobulin light chain enhancer, which is most active in murine B cells in late developmental stages. These mice developed nonmalignant...

An interesting feature of Bcl-xL protein is the presence of an unstructured loop domain between α1 and α2 helices, a domain not essential for its anti-apoptotic function and absent in CED-9 protein. Within this domain, Bcl-xL undergoes dynamic phosphorylation and dephosphorylation at Ser49 and Ser62 during G2 and mitosis in human cells. Studies have revealed that when these residues are mutated...

Reversing drug resistance with concurrent treatment confers anticancer benefits. In this study, we investigated the potential mechanism of glucosylceramide synthase (GCS)-mediated vinca alkaloid vinorelbine (VNR) resistance in human lung adenocarcinoma cells. Compared with PC14PE6/AS2 (AS2) and CL1-0 cells, apoptotic analysis showed that both A549 and CL1-5 cells were VNR-resistant, while these...

Restenosis after intraluminal or open vascular reconstruction remains an important clinical problem. Vascular endothelial cell (EC) injury induced by oxidative stress plays an important role in the development of intimal hyperplasia. In this study, we sought to evaluate the protective effects of Bcl-xl overexpression in vitro on oxidative stress-induced EC injury and the role of the Akt/endothe...

BCL-2 family proteins are known to regulate cell death during development by influencing the permeability of mitochondrial membranes. The anti-apoptotic BCL-2 family protein BCL-xL is highly expressed in the adult brain and localizes to mitochondria in the presynaptic terminal of the adult squid stellate ganglion. Application of recombinant BCL-xL through a patch pipette to mitochondria inside ...

Anti-apoptotic Bcl-2 and Bcl-xL are proposed to regulate starvation-induced autophagy by directly interacting with Beclin 1. Beclin 1 is also thought to be involved in multiple vesicle trafficking pathways such as endocytosis by binding to Atg14L and UVRAG. However, how the interaction of Bcl-2 family proteins and Beclin 1 regulates anti-bacterial autophagy (xenophagy) is still unclear. In this...

Emerging evidences suggest that transcription-independent mechanism of p53 appears to make an important contribution to the overall p53-dependent apoptosis. Recently, it has been postulated that the DNA-binding domain of p53 can interact with Bcl-Xl, and subsequently the proposed molecular interaction has been shown by NMR studies. Interestingly, Chipuk et al. [Cancer Cell 4 (2003) 371] reporte...