PMID- 26437781
OWN - NLM
STAT- MEDLINE
DCOM- 20160719
LR  - 20181113
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Linking)
VI  - 30
IP  - 3
DP  - 2016 Mar
TI  - A20 targets caspase-8 and FADD to protect HTLV-I-infected cells.
PG  - 716-27
LID - 10.1038/leu.2015.267 [doi]
AB  - Adult T-cell leukemia (ATL) arises from a human T-cell leukemia virus type I 
      (HTLV-I)-infected cell and has few therapeutic options. Here, we have uncovered a 
      previously unrecognized role for a ubiquitin-editing enzyme A20 in the survival 
      of HTLV-I-infected cells. Unlike in lymphomas of the B-cell lineage, A20 is 
      abundantly expressed in primary ATL cells without notable mutations. Depletion of 
      A20 in HTLV-I-infected cells resulted in caspase activation, cell death induction 
      and impaired tumorigenicity in mouse xenograft models. Mechanistically, A20 
      stably interacts with caspase-8 and Fas-associated via death domain (FADD) in 
      HTLV-I-infected cells. Mutational studies revealed that A20 supports the growth 
      of HTLV-I-infected cells independent of its catalytic functions and that the 
      zinc-finger domains are required for the interaction with and regulation of 
      caspases. These results indicate a pivotal role for A20 in the survival of 
      HTLV-I-infected cells and implicate A20 as a potential therapeutic target in ATL.
FAU - Saitoh, Y
AU  - Saitoh Y
AD  - Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and 
      Dental University, Tokyo, Japan.
FAU - Hamano, A
AU  - Hamano A
AD  - Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and 
      Dental University, Tokyo, Japan.
FAU - Mochida, K
AU  - Mochida K
AD  - Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and 
      Dental University, Tokyo, Japan.
FAU - Kakeya, A
AU  - Kakeya A
AD  - Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and 
      Dental University, Tokyo, Japan.
FAU - Uno, M
AU  - Uno M
AD  - Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and 
      Dental University, Tokyo, Japan.
AD  - Department of Comprehensive Reproductive Medicine, Tokyo Medical and Dental 
      University, Tokyo, Japan.
FAU - Tsuruyama, E
AU  - Tsuruyama E
AD  - Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and 
      Dental University, Tokyo, Japan.
FAU - Ichikawa, H
AU  - Ichikawa H
AD  - Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and 
      Dental University, Tokyo, Japan.
FAU - Tokunaga, F
AU  - Tokunaga F
AD  - Laboratory of Molecular Cell Biology, Institute for Molecular and Cellular 
      Regulation, Gunma University, Maebashi, Gunma, Japan.
FAU - Utsunomiya, A
AU  - Utsunomiya A
AD  - Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Japan.
FAU - Watanabe, T
AU  - Watanabe T
AD  - Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The 
      University of Tokyo, Tokyo, Japan.
FAU - Yamaoka, S
AU  - Yamaoka S
AD  - Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and 
      Dental University, Tokyo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151006
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (FADD protein, human)
RN  - 0 (Fas-Associated Death Domain Protein)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - EC 3.4.19.12 (TNFAIP3 protein, human)
RN  - EC 3.4.19.12 (Tumor Necrosis Factor alpha-Induced Protein 3)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 7)
RN  - EC 3.4.22.- (Caspase 8)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Caspase 3/genetics/metabolism
MH  - Caspase 7/genetics/metabolism
MH  - Caspase 8/*genetics/metabolism
MH  - Cell Death
MH  - Cell Line
MH  - DNA-Binding Proteins/antagonists & inhibitors/*genetics/metabolism
MH  - Fas-Associated Death Domain Protein/*genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation, Leukemic
MH  - Genetic Vectors
MH  - HEK293 Cells
MH  - Host-Pathogen Interactions
MH  - Human T-lymphotropic virus 1/*genetics/pathogenicity
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/antagonists & 
      inhibitors/*genetics/metabolism
MH  - Lentivirus/genetics
MH  - Leukemia-Lymphoma, Adult T-Cell/*genetics/metabolism/pathology/virology
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Neoplasm Transplantation
MH  - Nuclear Proteins/antagonists & inhibitors/*genetics/metabolism
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Signal Transduction
MH  - Tumor Burden
MH  - Tumor Necrosis Factor alpha-Induced Protein 3
EDAT- 2015/10/07 06:00
MHDA- 2016/07/20 06:00
CRDT- 2015/10/07 06:00
PHST- 2015/02/27 00:00 [received]
PHST- 2015/08/31 00:00 [revised]
PHST- 2015/09/18 00:00 [accepted]
PHST- 2015/10/07 06:00 [entrez]
PHST- 2015/10/07 06:00 [pubmed]
PHST- 2016/07/20 06:00 [medline]
AID - leu2015267 [pii]
AID - 10.1038/leu.2015.267 [doi]
PST - ppublish
SO  - Leukemia. 2016 Mar;30(3):716-27. doi: 10.1038/leu.2015.267. Epub 2015 Oct 6.