E3 ubiquitin ligases SIAH1/2 regulate hypoxiainducible factor-1 (HIF-1)-mediated Th17 cell differentiation

Akiko Matsui-Hasumi, Yayoi Sato, Ayako Uto-Konomi, Satoshi Yamashita, Junji Uehori, Akihiko Yoshimura, Masakatsu Yamashita, Hiroshi Asahara, Shinobu Suzuki, Masato Kubo

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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- 1a (HIF-1a) protein, which is reported to directly regulate expression of Il17a and Rorgt at the transcriptional level. In the absence of HIF-1a, 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-1a protein.

Original languageEnglish
Article numberdxx014
Pages (from-to)133-143
Number of pages11
JournalInternational Immunology
Volume29
Issue number3
DOIs
Publication statusPublished - 2017 Mar 1

Fingerprint

Th17 Cells
Ubiquitin-Protein Ligases
Cell Differentiation
Interleukin-17
Ligases
Ubiquitin
Autoimmunity
Gene Library
Proteins
Clone Cells
Cytokines
T-Lymphocytes
Cell Line
Hypoxia

Keywords

  • Autoimmune
  • HIF-1
  • Signaling
  • T17

ASJC Scopus subject areas

  • Immunology

Cite this

Matsui-Hasumi, A., Sato, Y., Uto-Konomi, A., Yamashita, S., Uehori, J., Yoshimura, A., ... Kubo, M. (2017). E3 ubiquitin ligases SIAH1/2 regulate hypoxiainducible factor-1 (HIF-1)-mediated Th17 cell differentiation. International Immunology, 29(3), 133-143. [dxx014]. https://doi.org/10.1093/intimm/dxx014

E3 ubiquitin ligases SIAH1/2 regulate hypoxiainducible factor-1 (HIF-1)-mediated Th17 cell differentiation. / Matsui-Hasumi, Akiko; Sato, Yayoi; Uto-Konomi, Ayako; Yamashita, Satoshi; Uehori, Junji; Yoshimura, Akihiko; Yamashita, Masakatsu; Asahara, Hiroshi; Suzuki, Shinobu; Kubo, Masato.

In: International Immunology, Vol. 29, No. 3, dxx014, 01.03.2017, p. 133-143.

Research output: Contribution to journalArticle

Matsui-Hasumi, A, Sato, Y, Uto-Konomi, A, Yamashita, S, Uehori, J, Yoshimura, A, Yamashita, M, Asahara, H, Suzuki, S & Kubo, M 2017, 'E3 ubiquitin ligases SIAH1/2 regulate hypoxiainducible factor-1 (HIF-1)-mediated Th17 cell differentiation', International Immunology, vol. 29, no. 3, dxx014, pp. 133-143. https://doi.org/10.1093/intimm/dxx014
Matsui-Hasumi, Akiko ; Sato, Yayoi ; Uto-Konomi, Ayako ; Yamashita, Satoshi ; Uehori, Junji ; Yoshimura, Akihiko ; Yamashita, Masakatsu ; Asahara, Hiroshi ; Suzuki, Shinobu ; Kubo, Masato. / E3 ubiquitin ligases SIAH1/2 regulate hypoxiainducible factor-1 (HIF-1)-mediated Th17 cell differentiation. In: International Immunology. 2017 ; Vol. 29, No. 3. pp. 133-143.
@article{6182b4a0a794436e8df2319c7c6030c4,
title = "E3 ubiquitin ligases SIAH1/2 regulate hypoxiainducible factor-1 (HIF-1)-mediated Th17 cell differentiation",
abstract = "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- 1a (HIF-1a) protein, which is reported to directly regulate expression of Il17a and Rorgt at the transcriptional level. In the absence of HIF-1a, 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-1a protein.",
keywords = "Autoimmune, HIF-1, Signaling, T17",
author = "Akiko Matsui-Hasumi and Yayoi Sato and Ayako Uto-Konomi and Satoshi Yamashita and Junji Uehori and Akihiko Yoshimura and Masakatsu Yamashita and Hiroshi Asahara and Shinobu Suzuki and Masato Kubo",
year = "2017",
month = "3",
day = "1",
doi = "10.1093/intimm/dxx014",
language = "English",
volume = "29",
pages = "133--143",
journal = "International Immunology",
issn = "0953-8178",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - E3 ubiquitin ligases SIAH1/2 regulate hypoxiainducible factor-1 (HIF-1)-mediated Th17 cell differentiation

AU - Matsui-Hasumi, Akiko

AU - Sato, Yayoi

AU - Uto-Konomi, Ayako

AU - Yamashita, Satoshi

AU - Uehori, Junji

AU - Yoshimura, Akihiko

AU - Yamashita, Masakatsu

AU - Asahara, Hiroshi

AU - Suzuki, Shinobu

AU - Kubo, Masato

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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- 1a (HIF-1a) protein, which is reported to directly regulate expression of Il17a and Rorgt at the transcriptional level. In the absence of HIF-1a, 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-1a protein.

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- 1a (HIF-1a) protein, which is reported to directly regulate expression of Il17a and Rorgt at the transcriptional level. In the absence of HIF-1a, 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-1a protein.

KW - Autoimmune

KW - HIF-1

KW - Signaling

KW - T17

UR - http://www.scopus.com/inward/record.url?scp=85019150567&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019150567&partnerID=8YFLogxK

U2 - 10.1093/intimm/dxx014

DO - 10.1093/intimm/dxx014

M3 - Article

C2 - 28338984

AN - SCOPUS:85019150567

VL - 29

SP - 133

EP - 143

JO - International Immunology

JF - International Immunology

SN - 0953-8178

IS - 3

M1 - dxx014

ER -