https://www.cell.com/cell/pdf/S0092-8674(00)80434-1.pdf

Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade

Apoptosis is a cell suicide mechanism that enables metazoans to control cell number in tissues and to eliminate individual cells that threaten the animal's survival. Certain cells have unique sensors, termed death receptors, on their surface. Death receptors detect the presence of extracellular death signals and, in response, they rapidly ignite the cell's intrinsic apoptosis machinery.

/pdf/death-receptors-signaling-and-modulation-yjd5e96rtz.pdf

Death receptors: signaling and modulation

Induction of apoptotic program in cell-free extracts : requirement for datp and cytochrome c

Bcl-2 is an integral membrane protein located mainly on the outer membrane of mitochondria. Overexpression of Bcl-2 prevents cells from undergoing apoptosis in response to a variety of stimuli. Cytosolic cytochrome c is necessary for the initiation of the apoptotic program, suggesting a possible connection between Bcl-2 and cytochrome c, which is normally located in the mitochondrial intermembrane space. Cells undergoing apoptosis were found to have an elevation of cytochrome c in the cytosol and a corresponding decrease in the mitochondria. Overexpression of Bcl-2 prevented the efflux of cytochrome c from the mitochondria and the initiation of apoptosis. Thus, one possible role of Bcl-2 in prevention of apoptosis is to block cytochrome c release from mitochondria.

https://science.sciencemag.org/content/sci/275/5303/1129.full.pdf

Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked

Cell Death: Critical Control Points

Yama/CPP32β, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase

The Baculovirus p35 Protein Inhibits Fas- and Tumor Necrosis Factor-induced Apoptosis

CrmA-inhibitable Cleavage of the 70-kDa Protein Component of the U1 Small Nuclear Ribonucleoprotein during Fas- and Tumor Necrosis Factor-induced Apoptosis

Bcl-x L , a prosurvival member of the Bcl-2 family that is expressed in many tumors, represses apoptosis induced by chemotherapeutic drugs in vitro . However, the contribution of apoptosis and prosurvival Bcl-2-related proteins to chemotherapy resistance in vivo is unknown and has been challenged by recent results with clonogenic survival assays. To test the ability of Bcl-x L to provide chemotherapy resistance to tumors, we transfected the mouse bcl-x L gene into the tumorigenic SCK mammary cell line and assessed the response of tumor cells to chemotherapeutic drugs in clonogenic assays and in a syngeneic mouse model. Bcl-x L conferred protection on SCK cells against methotrexate at certain drug concentrations, but not at all against 5-fluorouracil in clonogenic survival assays in vitro . Injection of SCK cells transfected with Bcl-x L or control plasmid in the mammary fat pads of syngeneic recipient mice resulted in tumors of similar size. However, although the volume of control tumors regressed up to 80% after 4 to 5 days of chemotherapy, SCK tumors expressing Bcl-x L did not regress and continued to grow in the presence of methotrexate or 5-fluorouracil. In addition, numbers of apoptotic cells were significantly higher in control tumors as compared to Bcl-x L -expressing tumors in animals treated with methotrexate or 5-fluorouracil. These results provide evidence that inhibition of apoptosis through Bcl-x L overexpression can promote resistance to chemotherapy in tumors in vivo .

/pdf/overexpression-of-bcl-xl-promotes-chemotherapy-resistance-of-3uijcqj240.pdf

David R. Beidler

Papers

Yama/CPP32β, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase

The Baculovirus p35 Protein Inhibits Fas- and Tumor Necrosis Factor-induced Apoptosis

CrmA-inhibitable Cleavage of the 70-kDa Protein Component of the U1 Small Nuclear Ribonucleoprotein during Fas- and Tumor Necrosis Factor-induced Apoptosis

Overexpression of Bcl-xL Promotes Chemotherapy Resistance of Mammary Tumors in a Syngeneic Mouse Model

Inhibition of protein synthesis by didemnin B is not sufficient to induce apoptosis in human mammary carcinoma (MCF7) cells