Caspase-3 mediated cleavage of BRCA1 during UV-induced apoptosis. 2002

Qimin Zhan, and Shunqian Jin, and Bobby Ng, and Jordan Plisket, and Sanjeev Shangary, and Abhilasha Rathi, and Kevin D Brown, and Rajasekaran Baskaran
Department of Molecular Genetics and Biochemistry, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, PA 15261, USA.

The breast cancer suppressor protein, BRCA1 plays an important role in mediating cell cycle arrest, apoptosis and DNA responses to DNA damage signals. In this study, we show that BRCA1 level is downregulated during UV-induced apoptosis by caspase-3 mediated cleavage. Cleavage of BRCA1 by caspase-3 produced a fragment that contained the C-terminal of the molecule. Accordingly, treatment of cells with caspase-3 inhibitor or mutation of a specific caspase-3 cleavage site (DLLD) at amino acid 1151-1154 of BRCA1 abolished cleavage and consequential accumulation of the BRCA1 C-terminal fragment. Whereas expression of the non-cleavable BRCA1 (D/A 1154) mutant conferred the resistance phenotype to UV-induced cell death, expression of the cleaved BRCA1 C-terminus induced cell death in the absence of UV. Examination of the mechanism of C-terminus-induced cell death revealed that the cleaved fragment triggers the apoptotic response through activation of BRCA1 downstream effectors, GADD45 and JNK. Altogether, results of our study demonstrate a functional role for caspase-3 mediated cleavage of BRCA1 during UV-induced apoptosis.

UI MeSH Term Description Entries
D010957 Plasmids Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS. Episomes,Episome,Plasmid
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005455 Fluorescent Antibody Technique Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy. Antinuclear Antibody Test, Fluorescent,Coon's Technique,Fluorescent Antinuclear Antibody Test,Fluorescent Protein Tracing,Immunofluorescence Technique,Coon's Technic,Fluorescent Antibody Technic,Immunofluorescence,Immunofluorescence Technic,Antibody Technic, Fluorescent,Antibody Technics, Fluorescent,Antibody Technique, Fluorescent,Antibody Techniques, Fluorescent,Coon Technic,Coon Technique,Coons Technic,Coons Technique,Fluorescent Antibody Technics,Fluorescent Antibody Techniques,Fluorescent Protein Tracings,Immunofluorescence Technics,Immunofluorescence Techniques,Protein Tracing, Fluorescent,Protein Tracings, Fluorescent,Technic, Coon's,Technic, Fluorescent Antibody,Technic, Immunofluorescence,Technics, Fluorescent Antibody,Technics, Immunofluorescence,Technique, Coon's,Technique, Fluorescent Antibody,Technique, Immunofluorescence,Techniques, Fluorescent Antibody,Techniques, Immunofluorescence,Tracing, Fluorescent Protein,Tracings, Fluorescent Protein
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000097642 GADD45 Proteins Nuclear proteins that act as critical stress sensors that mediate various cellular responses, including DNA REPAIR; CELL CYCLE ARREST; and APOPTOSIS. GADD45G Protein,Gadd45 gamma Protein,Growth Arrest and DNA-Damage-Inducible 45 gamma Protein
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D014466 Ultraviolet Rays That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants. Actinic Rays,Black Light, Ultraviolet,UV Light,UV Radiation,Ultra-Violet Rays,Ultraviolet Light,Ultraviolet Radiation,Actinic Ray,Light, UV,Light, Ultraviolet,Radiation, UV,Radiation, Ultraviolet,Ray, Actinic,Ray, Ultra-Violet,Ray, Ultraviolet,Ultra Violet Rays,Ultra-Violet Ray,Ultraviolet Black Light,Ultraviolet Black Lights,Ultraviolet Radiations,Ultraviolet Ray

Related Publications

Qimin Zhan, and Shunqian Jin, and Bobby Ng, and Jordan Plisket, and Sanjeev Shangary, and Abhilasha Rathi, and Kevin D Brown, and Rajasekaran Baskaran
December 2005, Cancer research,
Qimin Zhan, and Shunqian Jin, and Bobby Ng, and Jordan Plisket, and Sanjeev Shangary, and Abhilasha Rathi, and Kevin D Brown, and Rajasekaran Baskaran
September 2003, Oncogene,
Qimin Zhan, and Shunqian Jin, and Bobby Ng, and Jordan Plisket, and Sanjeev Shangary, and Abhilasha Rathi, and Kevin D Brown, and Rajasekaran Baskaran
April 1999, The Journal of biological chemistry,
Qimin Zhan, and Shunqian Jin, and Bobby Ng, and Jordan Plisket, and Sanjeev Shangary, and Abhilasha Rathi, and Kevin D Brown, and Rajasekaran Baskaran
February 2008, Apoptosis : an international journal on programmed cell death,
Qimin Zhan, and Shunqian Jin, and Bobby Ng, and Jordan Plisket, and Sanjeev Shangary, and Abhilasha Rathi, and Kevin D Brown, and Rajasekaran Baskaran
July 2003, Biochemical and biophysical research communications,
Qimin Zhan, and Shunqian Jin, and Bobby Ng, and Jordan Plisket, and Sanjeev Shangary, and Abhilasha Rathi, and Kevin D Brown, and Rajasekaran Baskaran
November 2002, Nihon yakurigaku zasshi. Folia pharmacologica Japonica,
Qimin Zhan, and Shunqian Jin, and Bobby Ng, and Jordan Plisket, and Sanjeev Shangary, and Abhilasha Rathi, and Kevin D Brown, and Rajasekaran Baskaran
March 2013, Biochemical and biophysical research communications,
Qimin Zhan, and Shunqian Jin, and Bobby Ng, and Jordan Plisket, and Sanjeev Shangary, and Abhilasha Rathi, and Kevin D Brown, and Rajasekaran Baskaran
June 2005, Oncogene,
Qimin Zhan, and Shunqian Jin, and Bobby Ng, and Jordan Plisket, and Sanjeev Shangary, and Abhilasha Rathi, and Kevin D Brown, and Rajasekaran Baskaran
March 2004, Cell death and differentiation,
Qimin Zhan, and Shunqian Jin, and Bobby Ng, and Jordan Plisket, and Sanjeev Shangary, and Abhilasha Rathi, and Kevin D Brown, and Rajasekaran Baskaran
July 2005, Cancer research,
Copied contents to your clipboard!