title: Histone H4 is cleaved by granzyme A during staurosporine-induced cell death in B-lymphoid Raji cells.
abstract: Granzyme A (GzmA) was first identified as a cytotoxic T lymphocyte protease protein with limited tissue expression. A number of cellular proteins are known to be cleaved by GzmA, and its function is to induce apoptosis. Histones H1, H2B, and H3 were identified as GzmA substrates during apoptotic cell death. Here, we demonstrated that histone H4 was cleaved by GzmA during staurosporine-induced cell death; however, in the presence of caspase inhibitors, staurosporine-treated Raji cells underwent necroptosis instead of apoptosis. Furthermore, histone H4 cleavage was blocked by the GzmA inhibitor nafamostat mesylate and by GzmA knockdown using siRNA. These results suggest that histone H4 is a novel substrate for GzmA in staurosporine-induced cells. [BMB Reports 2016; 49(10): 560-565].
authors.affiliation: Disease Target Structure Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141; Division of Life Sciences, Korea University, Seoul 02841, Korea.
authors.forename: Phil Young
authors.initials: PY
authors.lastname: Lee
authors.affiliation: Disease Target Structure Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Park
authors.affiliation: Disease Target Structure Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.
authors.forename: Seung Wook
authors.initials: SW
authors.lastname: Chi
authors.affiliation: Metabolic Regulation Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.
authors.forename: Kwang-Hee
authors.initials: KH
authors.lastname: Bae
authors.affiliation: Disease Target Structure Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.
authors.forename: Sunhong
authors.initials: S
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 06974, Korea University, Seoul 02841, Korea.
authors.forename: Sayeon
authors.initials: S
authors.lastname: Cho
authors.affiliation: Division of Life Sciences, Korea University, Seoul 02841, Korea.
authors.forename: Seongman
authors.initials: S
authors.lastname: Kang
authors.affiliation: Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Disease Target Structure Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.
authors.forename: Sung Goo
authors.initials: SG
authors.lastname: Park
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001550:Benzamidines; D015153:Blotting, Western; D061945:Caspase Inhibitors / Q000494:pharmacology; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D053804:Granzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D019311:Staurosporine / Q000494:pharmacology / Q000633:toxicity*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D001550:Benzamidines; D061945:Caspase Inhibitors; D006146:Guanidines; D006657:Histones; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D053804:Granzymes; D019311:Staurosporine; C032855:nafamostat