Histone H4 is cleaved by granzyme A during staurosporine-induced cell death in B-lymphoid Raji cells

Phil Young Lee; Byoung Chul Park; Seung Wook Chi; Kwang Hee Bae; Sunhong Kim; Sayeon Cho; Seongman Kang; Jeong Hoon Kim; Sung Goo Park

doi:10.5483/BMBRep.2016.49.10.105

Histone H4 is cleaved by granzyme A during staurosporine-induced cell death in B-lymphoid Raji cells

Phil Young Lee, Byoung Chul Park, Seung Wook Chi, Kwang Hee Bae, Sunhong Kim, Sayeon Cho, Seongman Kang, Jeong Hoon Kim, Sung Goo Park

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

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.

Original language	English
Pages (from-to)	560-565
Number of pages	6
Journal	BMB reports
Volume	49
Issue number	10
DOIs	https://doi.org/10.5483/BMBRep.2016.49.10.105
Publication status	Published - 2016

Bibliographical note

Funding Information:
This work was supported by KRIBB and a research grant from the National Research Foundation of Korea (NRF-2011-0028172).

Publisher Copyright:
© 2016 by the The Korean Society for Biochemistry and Molecular Biology.

Keywords

Caspase-independent cell death
Granzyme A
Histone H4
Raji cell

ASJC Scopus subject areas

Biochemistry
Molecular Biology

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10.5483/BMBRep.2016.49.10.105

Cite this

@article{09320a89fcec4bfa9eb2567104ad18ae,

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.",

keywords = "Caspase-independent cell death, Granzyme A, Histone H4, Raji cell",

author = "Lee, {Phil Young} and Park, {Byoung Chul} and Chi, {Seung Wook} and Bae, {Kwang Hee} and Sunhong Kim and Sayeon Cho and Seongman Kang and Kim, {Jeong Hoon} and Park, {Sung Goo}",

note = "Funding Information: This work was supported by KRIBB and a research grant from the National Research Foundation of Korea (NRF-2011-0028172). Publisher Copyright: {\textcopyright} 2016 by the The Korean Society for Biochemistry and Molecular Biology.",

year = "2016",

doi = "10.5483/BMBRep.2016.49.10.105",

language = "English",

volume = "49",

pages = "560--565",

journal = "BMB reports",

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publisher = "The Biochemical Society of the Republic of Korea",

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TY - JOUR

T1 - Histone H4 is cleaved by granzyme A during staurosporine-induced cell death in B-lymphoid Raji cells

AU - Lee, Phil Young

AU - Park, Byoung Chul

AU - Chi, Seung Wook

AU - Bae, Kwang Hee

AU - Kim, Sunhong

AU - Cho, Sayeon

AU - Kang, Seongman

AU - Kim, Jeong Hoon

AU - Park, Sung Goo

N1 - Funding Information: This work was supported by KRIBB and a research grant from the National Research Foundation of Korea (NRF-2011-0028172). Publisher Copyright: © 2016 by the The Korean Society for Biochemistry and Molecular Biology.

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Caspase-independent cell death

KW - Granzyme A

KW - Histone H4

KW - Raji cell

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DO - 10.5483/BMBRep.2016.49.10.105

M3 - Article

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SN - 1976-6696

VL - 49

SP - 560

EP - 565

JO - BMB reports

JF - BMB reports

IS - 10

ER -

Histone H4 is cleaved by granzyme A during staurosporine-induced cell death in B-lymphoid Raji cells

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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