PMID- 25119188
OWN - NLM
STAT- MEDLINE
DCOM- 20150723
LR  - 20240209
IS  - 1466-1268 (Electronic)
IS  - 1355-8145 (Print)
IS  - 1355-8145 (Linking)
VI  - 20
IP  - 1
DP  - 2015 Jan
TI  - Suberoylanilide hydroxamic acid induces ROS-mediated cleavage of HSP90 in 
      leukemia cells.
PG  - 149-57
LID - 10.1007/s12192-014-0533-4 [doi]
AB  - Heat shock protein 90 (HSP90) is a molecular chaperone that supports stability of 
      client proteins. We found that HSP90 was cleaved to 55 kDa protein after 
      treatment with histone deacetylase (HDAC) inhibitors including suberoylanilide 
      hydroxamic acid (SAHA) in several leukemia cell lines. We further analyzed 
      molecular changes induced by SAHA in K562 cells. The SAHA-induced cleavage of 
      HSP90 was blocked by a pan-caspase inhibitor, z-VAD-fmk, implying that the 
      process is dependent on caspase activity. However, the experiments using 
      antagonistic and agonistic Fas antibodies revealed that the cleavage of HSP90 was 
      not dependent on Fas signaling. SAHA induced generation of reactive oxygen 
      species (ROS), and the cleavage of HSP90 was blocked by a ROS scavenger 
      N-acetylcystein (NAC). We also confirmed that hydrogen peroxide (H2O2) induced 
      cleavage of HSP90 in a similar manner. Caspase 2, 3, 4, 6, 8, and 10 were 
      activated by treatment with SAHA, and the activities were reduced by the 
      pretreatment of NAC. Treatment of the cells with caspase 10 inhihitor, but not 
      other inhibitors of caspases activated by SAHA, prevented cleavage of HSP90 by 
      SAHA. SAHA-induced ROS generation and HSP90 cleavage were dependent on newly 
      synthesized unknown proteins. Taken together, our results suggest that the 
      cleavage of HSP90 by SAHA is mediated by ROS generation and caspase 10 
      activation. HSP90 cleavage may provide an additional mechanism involved in 
      anti-cancer effects of HDAC inhibitors.
FAU - Park, Sangkyu
AU  - Park S
AD  - Department of Biochemistry, College of Natural Sciences, Chungbuk National 
      University, Cheongju, Chungbuk, 361-763, Republic of Korea.
FAU - Park, Jeong-A
AU  - Park JA
FAU - Kim, Young-Eun
AU  - Kim YE
FAU - Song, Sukgil
AU  - Song S
FAU - Kwon, Hyung-Joo
AU  - Kwon HJ
FAU - Lee, Younghee
AU  - Lee Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140814
PL  - Netherlands
TA  - Cell Stress Chaperones
JT  - Cell stress & chaperones
JID - 9610925
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (FAS protein, human)
RN  - 0 (HSP90 Heat-Shock Proteins)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
RN  - 0 (fas Receptor)
RN  - 58IFB293JI (Vorinostat)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 3.4.22.- (Caspase 10)
RN  - EC 3.4.22.- (Caspases)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Amino Acid Chloromethyl Ketones/pharmacology
MH  - Caspase 10/metabolism
MH  - Caspase Inhibitors/pharmacology
MH  - Caspases/chemistry/metabolism
MH  - HSP90 Heat-Shock Proteins/*metabolism
MH  - Histone Deacetylase Inhibitors/pharmacology
MH  - Humans
MH  - Hydrogen Peroxide/pharmacology
MH  - Hydroxamic Acids/*pharmacology
MH  - K562 Cells
MH  - Leukemia
MH  - Proteolysis/drug effects
MH  - Reactive Oxygen Species/*metabolism
MH  - Signal Transduction/drug effects
MH  - Vorinostat
MH  - fas Receptor/immunology/metabolism
PMC - PMC4255254
EDAT- 2014/08/15 06:00
MHDA- 2015/07/24 06:00
PMCR- 2015/07/01
CRDT- 2014/08/15 06:00
PHST- 2014/02/24 00:00 [received]
PHST- 2014/07/29 00:00 [accepted]
PHST- 2014/07/03 00:00 [revised]
PHST- 2014/08/15 06:00 [entrez]
PHST- 2014/08/15 06:00 [pubmed]
PHST- 2015/07/24 06:00 [medline]
PHST- 2015/07/01 00:00 [pmc-release]
AID - S1355-8145(23)01590-0 [pii]
AID - 533 [pii]
AID - 10.1007/s12192-014-0533-4 [doi]
PST - ppublish
SO  - Cell Stress Chaperones. 2015 Jan;20(1):149-57. doi: 10.1007/s12192-014-0533-4. 
      Epub 2014 Aug 14.