BMB Rep. 2016; 49(10): 560-565  
Histone H4 is cleaved by granzyme A during staurosporine-induced cell death in B-lymphoid Raji cells
Phil Young Lee1,4, Byoung Chul Park1, Seung Wook Chi1, Kwang-Hee Bae2, Sunhong Kim1, Sayeon Cho3, Seongman Kang4, Jeong-Hoon Kim5,* & Sung Goo Park1,*
1Disease Target Structure Research Center, 2Metabolic Regulation Research Center, 5Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, 3College of Pharmacy, Chung-Ang University, Seoul 06974, 4Division of Life Sciences, Korea University, Seoul 02841, Korea
Correspondence to: Sung Goo Park, Tel: +82-42-860-4262; Fax: +82-42-860-4269; E-mail:, Jeong-Hoon Kim, Tel: +82-42-860-4264; Fax: +82-42-860-4269; E-mail:
Received: June 27, 2016; Revised: July 14, 2016; Accepted: July 20, 2016; Published online: October 31, 2016.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

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.
Keywords: Caspase-independent cell death, Granzyme A, Histone H4, Raji cell

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