PMID- 23708656
OWN - NLM
STAT- MEDLINE
DCOM- 20140709
LR  - 20231213
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 33
IP  - 18
DP  - 2014 May 1
TI  - HTLV-1 HBZ positively regulates the mTOR signaling pathway via inhibition of 
      GADD34 activity in the cytoplasm.
PG  - 2317-28
LID - 10.1038/onc.2013.181 [doi]
AB  - Human T-cell leukemia virus type-1 (HTLV-1) infection causes adult T-cell 
      leukemia (ATL). Modulation of the transcriptional control of cellular genes by 
      HTLV-1 is thought to be associated with the development of ATL. The viral protein 
      HTLV-1 basic leucine-zipper factor (HBZ) has been shown to dysregulate the 
      activity of cellular transcription factors. Here, we demonstrate that HBZ is 
      exported from the nucleus to the cytoplasm, where it activates the mammalian 
      target of rapamycin (mTOR) signaling pathway through an association with growth 
      arrest and DNA damage gene 34 (GADD34). The N-terminal region of HBZ interacts 
      with the C-terminal region of GADD34. HBZ contains a functional nuclear export 
      signal (NES) sequence within its N-terminal region and it is exported from the 
      nucleus via the CRM1-dependent pathway. Nuclear export of HBZ is essential for 
      its interaction with GADD34 and increased phosphorylation of S6 kinase, which is 
      an established downstream target of the mTOR pathway. Starvation-induced 
      autophagy is significantly suppressed by the overexpression of HBZ. These 
      findings indicate that HBZ is actively exported to the cytoplasm, where it 
      dysregulates the function of cellular factors.
FAU - Mukai, R
AU  - Mukai R
AD  - Faculty of Engineering, Tokushima Bunri University, Sanuki, Kagawa, Japan.
FAU - Ohshima, T
AU  - Ohshima T
AD  - 1] Faculty of Engineering, Tokushima Bunri University, Sanuki, Kagawa, Japan [2] 
      Faculty of Pharmaceutical Science at Kagawa Campus, Tokushima Bunri University, 
      Sanuki, Kagawa, Japan.
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130527
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Basic-Leucine Zipper Transcription Factors)
RN  - 0 (HBZ protein, human T-cell leukemia virus type I)
RN  - 0 (Karyopherins)
RN  - 0 (Nuclear Export Signals)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Retroviridae Proteins)
RN  - 0 (Viral Proteins)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.16 (PPP1R15A protein, human)
RN  - EC 3.1.3.16 (Protein Phosphatase 1)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Amino Acid Sequence
MH  - Animals
MH  - Autophagy
MH  - Basic-Leucine Zipper Transcription Factors/chemistry/genetics/*metabolism
MH  - Cell Nucleus/metabolism
MH  - Cytoplasm/*metabolism
MH  - HEK293 Cells
MH  - *Human T-lymphotropic virus 1
MH  - Humans
MH  - Karyopherins/metabolism
MH  - Leukemia-Lymphoma, Adult T-Cell/*metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - NIH 3T3 Cells
MH  - Nuclear Export Signals
MH  - Protein Phosphatase 1/chemistry/genetics/*metabolism
MH  - Protein Structure, Tertiary
MH  - Receptors, Cytoplasmic and Nuclear/metabolism
MH  - Retroviridae Proteins
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Transfection
MH  - Viral Proteins/chemistry/genetics/*metabolism
MH  - Exportin 1 Protein
EDAT- 2013/05/28 06:00
MHDA- 2014/07/10 06:00
CRDT- 2013/05/28 06:00
PHST- 2012/10/26 00:00 [received]
PHST- 2013/03/30 00:00 [revised]
PHST- 2013/04/01 00:00 [accepted]
PHST- 2013/05/28 06:00 [entrez]
PHST- 2013/05/28 06:00 [pubmed]
PHST- 2014/07/10 06:00 [medline]
AID - onc2013181 [pii]
AID - 10.1038/onc.2013.181 [doi]
PST - ppublish
SO  - Oncogene. 2014 May 1;33(18):2317-28. doi: 10.1038/onc.2013.181. Epub 2013 May 27.