PMID- 28338984
OWN - NLM
STAT- MEDLINE
DCOM- 20180101
LR  - 20180110
IS  - 1460-2377 (Electronic)
IS  - 0953-8178 (Linking)
VI  - 29
IP  - 3
DP  - 2017 Mar 1
TI  - E3 ubiquitin ligases SIAH1/2 regulate hypoxia-inducible factor-1 (HIF-1)-mediated 
      Th17 cell differentiation.
PG  - 133-143
LID - 10.1093/intimm/dxx014 [doi]
AB  - IL-17 is known to be a cytokine mainly secreted from Th17 cells, which well 
      associate with autoimmune inflammatory responses. In the generation of Th17 
      cells, RORc and RORa have pivotal roles in controlling the transcription of Il17. 
      We speculated additional regulation in Il17a transcription and randomly screened 
      a 6344 clone cDNA library to identify specific modulators for Il17a promoter 
      activity. After the screen, the E3 ubiquitin ligases SIAH1 and SIAH2 were 
      investigated further and confirmed to increase Il17a promoter activity in a 
      T-cell line and to promote Th17 development ex vivo. This enhancement was a 
      consequence of enhanced expression of hypoxia-inducible factor-1alpha (HIF-1alpha) 
      protein, which is reported to directly regulate expression of Il17a and Rorgt at 
      the transcriptional level. In the absence of HIF-1alpha, both ubiquitin ligases had 
      little effect on Th17 cell differentiation. These results suggest that the SIAH1 
      and SIAH2 play a pivotal role to promote Th17 cell differentiation through 
      maintaining the stability of HIF-1alpha protein.
CI  - (c) The Japanese Society for Immunology. 2017. All rights reserved. For 
      permissions, please e-mail: journals.permissions@oup.com.
FAU - Matsui-Hasumi, Akiko
AU  - Matsui-Hasumi A
AD  - Laboratory for Cytokine Regulation, RIKEN Center for Integrative Medical Sciences 
      (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama-shi, Kanagawa 230-0045, Japan.
AD  - Department of Molecular & Cellular Biology, Kobe Pharma Research Institute, 
      Nippon Boehringer Ingelheim Co., Ltd, 6-7-5 Minatojima-Minamimachi, Chuo-Ku, 
      Kobe-shi, Hyogo 650-0047, Japan.
FAU - Sato, Yayoi
AU  - Sato Y
AD  - Department of Molecular & Cellular Biology, Kobe Pharma Research Institute, 
      Nippon Boehringer Ingelheim Co., Ltd, 6-7-5 Minatojima-Minamimachi, Chuo-Ku, 
      Kobe-shi, Hyogo 650-0047, Japan.
FAU - Uto-Konomi, Ayako
AU  - Uto-Konomi A
AD  - Laboratory for Cytokine Regulation, RIKEN Center for Integrative Medical Sciences 
      (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama-shi, Kanagawa 230-0045, Japan.
AD  - Department of Molecular & Cellular Biology, Kobe Pharma Research Institute, 
      Nippon Boehringer Ingelheim Co., Ltd, 6-7-5 Minatojima-Minamimachi, Chuo-Ku, 
      Kobe-shi, Hyogo 650-0047, Japan.
FAU - Yamashita, Satoshi
AU  - Yamashita S
AD  - Department of Systems Biomedicine, National Research Institute for Child Health 
      and Development, 2-10-1 Okura, Setagaya-ku,Tokyo 157-8535, Japan.
FAU - Uehori, Junji
AU  - Uehori J
AD  - Department of Molecular & Cellular Biology, Kobe Pharma Research Institute, 
      Nippon Boehringer Ingelheim Co., Ltd, 6-7-5 Minatojima-Minamimachi, Chuo-Ku, 
      Kobe-shi, Hyogo 650-0047, Japan.
FAU - Yoshimura, Akihiko
AU  - Yoshimura A
AD  - Department of Microbiology and Immunology, Keio University School of Medicine, 35 
      Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
FAU - Yamashita, Masakatsu
AU  - Yamashita M
AD  - Department of Immunology, Graduate School of Medicine, Ehime University, 
      Shitsukawa, Toon-shi, Ehime 791-0295, Japan.
FAU - Asahara, Hiroshi
AU  - Asahara H
AD  - Department of Systems Biomedicine, National Research Institute for Child Health 
      and Development, 2-10-1 Okura, Setagaya-ku,Tokyo 157-8535, Japan.
AD  - Department of Systems BioMedicine, Tokyo Medical and Dental University, 1-5-45 
      Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
FAU - Suzuki, Shinobu
AU  - Suzuki S
AD  - Department of Molecular & Cellular Biology, Kobe Pharma Research Institute, 
      Nippon Boehringer Ingelheim Co., Ltd, 6-7-5 Minatojima-Minamimachi, Chuo-Ku, 
      Kobe-shi, Hyogo 650-0047, Japan.
FAU - Kubo, Masato
AU  - Kubo M
AD  - Laboratory for Cytokine Regulation, RIKEN Center for Integrative Medical Sciences 
      (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama-shi, Kanagawa 230-0045, Japan.
AD  - Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo 
      University of Science, 2669 Yamazaki, Noda-shi, Chiba 278-0022, Japan.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Animals
MH  - *Cell Differentiation
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/deficiency/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Th17 Cells/*cytology/*metabolism
MH  - Ubiquitin-Protein Ligases/genetics/*metabolism
OTO - NOTNLM
OT  - HIF-1
OT  - Th17
OT  - autoimmune
OT  - signaling
EDAT- 2017/03/25 06:00
MHDA- 2018/01/02 06:00
CRDT- 2017/03/25 06:00
PHST- 2017/01/09 00:00 [received]
PHST- 2017/03/16 00:00 [accepted]
PHST- 2017/03/25 06:00 [pubmed]
PHST- 2018/01/02 06:00 [medline]
PHST- 2017/03/25 06:00 [entrez]
AID - 3074123 [pii]
AID - 10.1093/intimm/dxx014 [doi]
PST - ppublish
SO  - Int Immunol. 2017 Mar 1;29(3):133-143. doi: 10.1093/intimm/dxx014.