Targeting Bcl-2/Bcl-XL induces antitumor activity in uveal melanoma patient-derived xenografts.
PLoS ONE 9(1):e80836 (2014)
Uveal melanoma (UM) is associated with a high risk of metastases and lack of efficient therapies. Reduced capacity for apoptosis induction by chemotherapies is one obstacle to efficient treatments. Human UM is characterized by high expression of the anti-apoptotic protein Bcl-2. Consequently, re...
Decoding and unlocking the BCL-2 dependency of cancer cells.
Nature Reviews: Cancer 13(7):455 (2013)
Cancer cells are subject to many apoptotic stimuli that would kill them were it not for compensatory prosurvival alterations. BCL-2-like (BCL-2L) proteins contribute to such aberrant behaviour by engaging a network of interactions that is potent at promoting survival but that is also fragile: in...
C-terminal residues regulate localization and function of the antiapoptotic protein Bfl-1.
Journal of Biological Chemistry 284(44):30257 (2009)
Unlike other antiapoptotic members of the Bcl-2 family, Bfl-1 does not contain a well defined C-terminal transmembrane domain, and whether the C-terminal tail of Bfl-1 functions as a membrane anchor is not yet clearly established. The molecular modeling study of the full-length Bfl-1 performed w...
Bax activation by the BH3-only protein Puma promotes cell dependence on antiapoptotic Bcl-2 family members.
Journal of Cell Biology 185(2):279 (2009)
It is still unclear whether the BH3-only protein Puma (p53 up-regulated modulator of apoptosis) can prime cells to death and render antiapoptotic BH3-binding Bcl-2 homologues necessary for survival through its ability to directly interact with proapoptotic Bax and activate it. In this study, we ...
Cell cycle-dependent induction of autophagy, mitophagy and reticulophagy.
Cell Cycle 6(18):2263 (2007)
When added to cells, a variety of autophagy inducers that operate through distinct mechanisms and target different organelles for autophagic destruction (mitochondria in mitophagy, endoplasmic reticulum in reticulophagy) rarely induce autophagic vacuolization in more than 50% or the cells. Here ...
Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1.
EMBO Journal 26(10):2527 (2007)
The anti-apoptotic proteins Bcl-2 and Bcl-X(L) bind and inhibit Beclin-1, an essential mediator of autophagy. Here, we demonstrate that this interaction involves a BH3 domain within Beclin-1 (residues 114-123). The physical interaction between Beclin-1 and Bcl-X(L) is lost when the BH3 domain of...
BH3-only proteins and BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin 1 and Bcl-2/Bcl-X(L).
Autophagy 3(4):374 (2007)
Beclin 1 has recently been identified as novel BH3-only protein, meaning that it carries one Bcl-2-homology-3 (BH3) domain. As other BH3-only proteins, Beclin 1 interacts with anti-apoptotic multidomain proteins of the Bcl-2 family (in particular Bcl-2 and its homologue Bcl-X(L)) by virtue of it...
A simple theoretical model for fluorescence polarization binding assay development.
Journal of Biomolecular Screening 11(8):949 (2006)
Fluorescence polarization is a screening technology that is radioactivity free, homogeneous, and ratiometric. The signal measured with this technology is a weighted value of free and bound ligand. As a consequence, saturation curves are accessible only after calculation of the corresponding conc...
The small organic compound HA14-1 prevents Bcl-2 interaction with Bax to sensitize malignant glioma cells to induction of cell death.
Cancer Research 66(5):2757 (2006)
A functional imbalance between proapoptotic Bax and antiapoptotic Bcl-2 is likely to participate in the resistance of cancer cells to therapy. We show here that ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (HA14-1), a small organic compound recently proposed to...
[The Bcl-2 family of proteins as drug targets].
Journal de la Société de Biologie 199(3):253 (2005)
Programmed cell death or apoptosis is a crucial process for normal embryonic development and homeostasis. Apoptosis is known to be coupled to multiple signalling pathways. Identification of critical points in the regulation of apoptosis is of major interest both for the understanding of control ...
Shooting at survivors: Bcl-2 family members as drug targets for cancer.
Biochimica et Biophysica Acta 1644(2-3):251 (2004)
LIM kinase and Diaphanous cooperate to regulate serum response factor and actin dynamics.
Journal of Cell Biology 157(5):831 (2002)
The small GTPase RhoA controls activity of serum response factor (SRF) by inducing changes in actin dynamics. We show that in PC12 cells, activation of SRF after serum stimulation is RhoA dependent, requiring both actin polymerization and the Rho kinase (ROCK)-LIM kinase (LIMK)-cofilin signaling...
Activation of SRF-Regulated Chromosomal Templates by Rho-Family GTPases Requires a Signal that Also Induces H4 Hyperacetylation
Cell 92(4):475 (1998)
Constitutively active forms of the small GTPases RhoA (RhoA.V14) and Cdc42 (Cdc42.V12) induce expression of extrachromosomal SRF reporter genes in microinjection experiments, but only Cdc42.V12 can efficiently activate a chromosomal template. Both SAPK/JNK-dependent or -independent signals ...
Comparison of hamster and mouse reveals interspecies differences in the regulation of hepatic CYP2A isozymes
Biochemical Pharmacology 46(10):1681 (1993)
Three CYP2A-related activities [coumarin 7-hydroxylase (COH), testosterone 7α- (test7α) and 15α-hydroxylases (test15α)], identified in hamster liver and analysed by immunoinhibition, and western and northern blotting, were found to be similar to mouse and human CYP2As. In the microsomal fra...