Search results for "Bcl-2"
showing 10 items of 197 documents
Mcl-1 and Bok transmembrane domains : Unexpected players in the modulation of apoptosis
2020
The Bcl-2 protein family comprises both proand antiapoptotic members that control the permeabilization of the mitochondrial outer membrane, a crucial step in the modulation of apoptosis. Recent research has demonstrated that the carboxyl-terminal transmembrane domain (TMD) of some Bcl-2 protein family mem-bers can modulate apoptosis; however, the transmembrane interactome of the antiapoptotic protein Mcl-1 remains largely unexplored. Here, we demonstrate that the Mcl-1 TMD forms homooligomers in the mitochondrial membrane, competes with full-length Mcl-1 protein with regards to its antiapoptotic function, and induces cell death in a Bok-dependent manner. While the Bok TMD oligomers locate p…
Lack of NFATc1 SUMOylation prevents autoimmunity and alloreactivity
2020
A novel transgenic mouse, in which the transcription factor NFATc1 bears lysine-to-arginine mutations that prevent modification by SUMO, develops normally and is healthy. However, SUMO-insensitive NFATc1 transmits strong tolerogenic signals, thus preventing autoimmune and alloimmune T cell responses.
Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins
2017
Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensiti…
Characterizing BCL-2 family protein domains in membranes:insertion, interaction and apoptotic modulation roles
2015
El objetivo de mi tesis doctoral es el estudio de los dominios transmembrana (TMD) de las proteínas de la familia Bcl-2. La principal función de esta familia de proteínas es la regulación del proceso apoptótico (1,2). Para Ello, se establece un balance de interacciones proteína-proteína entre los miembros pro- y antiapoptóticos de esta familia proteica (3,4). Nuestra hipótesis de trabajo postula que los fragmentos transmembrana de dichas proteínas pueden estar implicados no sólo en su localización subcelular sino también en el establecimiento de la red de interacciones entre proteínas Bcl-2 así como en el desarrollo de su función apoptótica.. Para corroborar esta hipótesis, hemos analizado …
A double-negative (IgD−CD27−) B cell population is increased in the peripheral blood of elderly people
2009
The T cell branch of the immune system has been extensively studied in the elderly and it is known that the elderly have impaired immune function, mainly due to the chronic antigenic load that ultimately causes shrinkage of the T cell repertoire and filling of the immunologic space with memory T cells. In the present paper, we describe the IgD(-)CD27(-) double-negative B cell population which (as we have recently described) is higher in the elderly. Most of these cells were IgG(+). Evaluation of the telomere length and expression of the ABCB1 transporter and anti-apoptotic molecule, Bcl2, shows that they have the markers of memory B cells. We also show that these cells do not act as antigen…
Low bcl-2 expression and increased spontaneous apoptosis in T-lymphocytes from newly-diagnosed IDDM patients.
1995
The bcl-2 gene product has been shown to regulate apoptotic cell death, and its dysregulation has been shown to induce several abnormalities in the immune system. No data exist regarding bcl-2 expression in autoimmune diseases, such as human insulin-dependent diabetes mellitus (IDDM). We investigated bcl-2 protein expression by testing T lymphocytes from 15 newly-diagnosed (3 weeks) IDDM patients in comparison to 10 age-matched control subjects. The expression of bcl-2 on CD3+ lymphocyte subsets was investigated after membrane permeabilization by two- or three-colour immunofluorescence. When the percentage and mean fluorescence intensity (MFI) of bcl-2+/CD3+ cells from normal individuals an…
bcl-2 expression and prognosis in squamous-cell carcinomas of the esophagus
1996
The bcl-2 proto-oncogene is a known inhibitor of apoptosis and may be an important regulator of tumor growth. In the present study, bcl-2-protein expression was investigated by immunohistochemistry and correlated with prognosis in a series of 150 potentially curatively resected squamous-cell carcinomas of the esophagus. For comparison, bcl-2-protein expression was analyzed in normal esophageal mucosa, severe squamous dysplasias and carcinomas in situ. bcl-2 immunoreactivity was found in 40 out of 150 invasive squamous-cell carcinomas; the remaining carcinomas were completely negative. bcl-2-protein expression was found more frequently among poorly differentiated than among well-differentiat…
The behaviour of Bcl-2, Bax and Bcl-x in Darier's disease
2002
SummaryBackground Darier's disease (DD) is a rare autosomal dominant disorder of keratinization caused by a mutation of the ATP2A2 gene. There is little information on the behaviour of Bcl-2, Bax and Bcl-x in DD. Objectives To investigate the dynamic control and the behaviour of Bax, Bcl-2 and Bcl-x in DD. We asked whether members of the Bcl-2 family might manifest their effects through modulation of intracellular calcium signalling or whether the gene that encodes the sarco/endoplasmic reticulum Ca2+ ATPase isoform 2 (SERCA2) modulates the Bcl-2 family in the regulation of apoptosis in DD. Methods Immunohistochemical methods were used. Results There was no immunoreactivity for Bcl-2 and Bc…
A constitutive BCL2 down-regulation aggravates the phenotype of PKD1-mutant-induced polycystic kidney disease
2017
IF 5.340; International audience; The main identified function of BCL2 protein is to prevent cell death by apoptosis. Mice knock-out for Bcl2 demonstrate growth retardation, severe polycystic kidney disease (PKD), gray hair and lymphopenia, and die prematurely after birth. Here, we report a 40-year-old male referred to for abdominal and thoracic aortic dissection with associated aortic root aneurysm, PKD, lymphocytopenia with a history of T cell lymphoblastic lymphoma, white hair since the age of 20, and learning difficulties. PKD, which was also detected in the father and sister, was related to an inherited PKD1 mutation. The combination of PKD with gray hair and lymphocytopenia was also r…
Expression of Bax, a pro-apoptotic member of the Bcl-2 family, in esophageal squamous cell carcinoma
1997
Samples of normal esophageal squamous epithelium (n = 10), severe squamous cell dyplasia (n = 22), carcinoma in situ (n = 15), invasive squamous cell carcinoma (n = 172), lymph-node metastasis (n = 21) and 2 permanent esophageal squamous cell carcinoma cell lines were analyzed immunohistochemically for Bax expression using a polyclonal anti-Bax antibody. Immunostaining was evaluated according to a score system (0–8 points) based on the percentage of positive tumor cells and the relative immunostaining intensity. Cytoplasmatic staining for Bax protein was found uniformly in all cell layers of the normal esophageal squamous epithelium. In contrast, a gradual loss of immunoreactivity for Bax w…