PMID- 24920810
OWN - NLM
STAT- MEDLINE
DCOM- 20140925
LR  - 20211021
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 88
IP  - 16
DP  - 2014 Aug
TI  - Modulation of Kaposi's sarcoma-associated herpesvirus interleukin-6 function by 
      hypoxia-upregulated protein 1.
PG  - 9429-41
LID - 10.1128/JVI.00511-14 [doi]
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV, also called human herpesvirus 8) 
      is linked to the development of Kaposi's sarcoma (KS), primary effusion lymphoma 
      (PEL), and multicentric Castleman's disease (MCD). KSHV expresses several 
      proteins that modulate host cell signaling pathways. One of these proteins is 
      viral interleukin-6 (vIL-6), which is a homolog of human IL-6 (hIL-6). vIL-6 is 
      able to prevent apoptosis and promote proinflammatory signaling, angiogenesis, 
      and cell proliferation. Although it can be secreted, vIL-6 is mainly an 
      intracellular protein that is retained in the endoplasmic reticulum (ER). We 
      performed affinity purification and mass spectrometry to identify novel vIL-6 
      binding partners and found that a cellular ER chaperone, hypoxia-upregulated 
      protein 1 (HYOU1), interacts with vIL-6. Immunohistochemical staining reveals 
      that both PEL and KS tumor tissues express significant amounts of HYOU1. We also 
      show that HYOU1 increases endogenous vIL-6 protein levels and that HYOU1 
      facilitates vIL-6-induced JAK/STAT signaling, migration, and survival in 
      endothelial cells. Furthermore, our data suggest that HYOU1 also modulates 
      vIL-6's ability to induce CCL2, a chemokine involved in cell migration. Finally, 
      we investigated the impact of HYOU1 on cellular hIL-6 signaling. Collectively, 
      our data indicate that HYOU1 is important for vIL-6 function and may play a role 
      in the pathogenesis of KSHV-associated cancers. IMPORTANCE: KSHV vIL-6 is 
      detectable in all KSHV-associated malignancies and promotes tumorigenesis and 
      inflammation. We identified a cellular protein, called hypoxia-upregulated 
      protein 1 (HYOU1), that interacts with KSHV vIL-6 and is present in KSHV-infected 
      tumors. Our data suggest that HYOU1 facilitates the vIL-6-induced signaling, 
      migration, and survival of endothelial cells.
CI  - Copyright (c) 2014, American Society for Microbiology. All Rights Reserved.
FAU - Giffin, Louise
AU  - Giffin L
AD  - Lineberger Comprehensive Cancer Center and Department of Microbiology & 
      Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North 
      Carolina, USA.
FAU - Yan, Feng
AU  - Yan F
AD  - Department of Cell Biology and Physiology, University of North Carolina at Chapel 
      Hill, Chapel Hill, North Carolina, USA.
FAU - Ben Major, M
AU  - Ben Major M
AD  - Department of Cell Biology and Physiology, University of North Carolina at Chapel 
      Hill, Chapel Hill, North Carolina, USA.
FAU - Damania, Blossom
AU  - Damania B
AD  - Lineberger Comprehensive Cancer Center and Department of Microbiology & 
      Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North 
      Carolina, USA damania@med.unc.edu.
LA  - eng
GR  - P01 CA019014/CA/NCI NIH HHS/United States
GR  - R01 CA163217/CA/NCI NIH HHS/United States
GR  - T32 AI007419/AI/NIAID NIH HHS/United States
GR  - CA096500/CA/NCI NIH HHS/United States
GR  - DE018281/DE/NIDCR NIH HHS/United States
GR  - CA163217/CA/NCI NIH HHS/United States
GR  - T32 CA071341/CA/NCI NIH HHS/United States
GR  - T32-AI007419/AI/NIAID NIH HHS/United States
GR  - U19 AI107810/AI/NIAID NIH HHS/United States
GR  - DP2OD007149/OD/NIH HHS/United States
GR  - AI107810/AI/NIAID NIH HHS/United States
GR  - U19 AI109965/AI/NIAID NIH HHS/United States
GR  - T32-CA071341/CA/NCI NIH HHS/United States
GR  - DP2 OD007149/OD/NIH HHS/United States
GR  - AI109965/AI/NIAID NIH HHS/United States
GR  - R01 DE018281/DE/NIDCR NIH HHS/United States
GR  - R01 CA096500/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140611
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Interleukin-6)
RN  - 0 (STAT Transcription Factors)
RN  - 0 (Viral Proteins)
RN  - 0 (oxygen-regulated proteins)
RN  - EC 2.7.10.2 (Janus Kinases)
SB  - IM
EIN - J Virol. 2014 Nov;88(21):12932
MH  - Cell Line
MH  - Chemokine CCL2/metabolism
MH  - HEK293 Cells
MH  - HSP70 Heat-Shock Proteins/*metabolism
MH  - Herpesviridae Infections/metabolism
MH  - Herpesvirus 8, Human/*metabolism
MH  - Humans
MH  - Interleukin-6/*metabolism
MH  - Janus Kinases/metabolism
MH  - STAT Transcription Factors/metabolism
MH  - Sarcoma, Kaposi/metabolism/virology
MH  - Signal Transduction/physiology
MH  - Up-Regulation/physiology
MH  - Viral Proteins/*metabolism
PMC - PMC4136275
EDAT- 2014/06/13 06:00
MHDA- 2014/09/26 06:00
PMCR- 2015/02/01
CRDT- 2014/06/13 06:00
PHST- 2014/06/13 06:00 [entrez]
PHST- 2014/06/13 06:00 [pubmed]
PHST- 2014/09/26 06:00 [medline]
PHST- 2015/02/01 00:00 [pmc-release]
AID - JVI.00511-14 [pii]
AID - 00511-14 [pii]
AID - 10.1128/JVI.00511-14 [doi]
PST - ppublish
SO  - J Virol. 2014 Aug;88(16):9429-41. doi: 10.1128/JVI.00511-14. Epub 2014 Jun 11.