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A20 targets caspase-8 and FADD to protect HTLV-I-infected cells
- Source :
- Leukemia. 30(3)
- Publication Year :
- 2015
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Adult
Cancer Research
viruses
Fas-Associated Death Domain Protein
Genetic Vectors
Caspase 3
Caspase 8
Caspase 7
Cell Line
03 medical and health sciences
Mice
immune system diseases
Mice, Inbred NOD
hemic and lymphatic diseases
medicine
Animals
Humans
Leukemia-Lymphoma, Adult T-Cell
FADD
RNA, Small Interfering
Caspase
Tumor Necrosis Factor alpha-Induced Protein 3
Death domain
Human T-lymphotropic virus 1
biology
Cell Death
Gene Expression Regulation, Leukemic
HEK 293 cells
Lentivirus
Intracellular Signaling Peptides and Proteins
Nuclear Proteins
Hematology
medicine.disease
Tumor Burden
DNA-Binding Proteins
Leukemia
030104 developmental biology
HEK293 Cells
Oncology
Host-Pathogen Interactions
biology.protein
Cancer research
Female
Neoplasm Transplantation
Signal Transduction
Subjects
Details
- ISSN :
- 14765551
- Volume :
- 30
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Leukemia
- Accession number :
- edsair.doi.dedup.....979fcac6240d9b4858f8ea40a7d872df