title: Histone H3 is Digested by Granzyme A During Compromised Cell Death in the Raji Cells.
abstract: Granzyme A (GzmA) was identified as a cytotoxic T lymphocyte protease protein expressed in the nucleus. A number of nuclear proteins are well known as GzmA substrates, and GzmA is related with caspase-independent apoptosis. Histones H1, H2B, and H3 were identified as GzmA substrates through in vitro experiment with purified nucleosome. Here, we demonstrated that histone H3 was cleaved by GzmA in vivo during staurosporine-induced cell death. Moreover, histone H3 cleavage was blocked by the GzmA inhibitor nafamostat mesylate and by GzmA knockdown using siRNA. Taken together, we verified that histone H3 is a real substrate for GzmA in vivo in the Raji cells treated by staurosporin.
authors.affiliation: Functional Genomics Research Center, KRIBB, 305-806, Daejeon, Republic of Korea.
authors.forename: Phil Young
authors.initials: PY
authors.lastname: Lee
authors.affiliation: Functional Genomics Research Center, KRIBB, 305-806, Daejeon, Republic of Korea.
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Park
authors.affiliation: Functional Genomics Research Center, KRIBB, 305-806, Daejeon, Republic of Korea.
authors.forename: Seung Wook
authors.initials: SW
authors.lastname: Chi
authors.affiliation: Functional Genomics Research Center, KRIBB, 305-806, Daejeon, Republic of Korea.
authors.forename: Kwang-Hee
authors.initials: KH
authors.lastname: Bae
authors.affiliation: Incurable Diseases Therapeutics Reasearch Center, KRIBB, 305-806, Daejeon, Republic of Korea.
authors.forename: Sunhong
authors.initials: S
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Sayeon
authors.initials: S
authors.lastname: Cho
authors.affiliation: Epigenomics Research Center, KRIBB, 305-806, Daejeon, Republic of Korea.
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Functional Genomics Research Center, KRIBB, 305-806, Daejeon, Republic of Korea.
authors.forename: Sung Goo
authors.initials: SG
authors.lastname: Park
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects* / Q000201:enzymology*; D016923:Cell Death; D002460:Cell Line; D053804:Granzymes / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D019311:Staurosporine / Q000633:toxicity
chemical_list: D006657:Histones; D053804:Granzymes; D019311:Staurosporine
keywords: Caspase-independent cell death; granzyme A; histone H3