TY - JOUR
T1 - Ubc9 interacts with and SUMOylates the TCR adaptor SLP-76 for NFAT transcription in T Cells
AU - Xiong, Yiwei
AU - Yi, Yulan
AU - Wang, Yan
AU - Yang, Naiqi
AU - Rudd, Christopher E.
AU - Liu, Hebin
N1 - Funding Information:
This work was supported by grants from the National Natural Science Foundation of China (31470840 to H.L.) and the Suzhou Key Program Special Fund (KSF-E-30 to H.L.).
Publisher Copyright:
© 2019 by The American Association of Immunologists, Inc.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Although the immune adaptor SH2 domain containing leukocyte phosphoprotein of 76 kDa (SLP-76) integrates and propagates the TCR signaling, the regulation of SLP-76 during the TCR signaling is incompletely studied. In this article, we report that SLP- 76 interacts with the small ubiquitin-like modifier (SUMO) E2 conjugase Ubc9 and is a substrate for Ubc9-mediated SUMOylation in human and mouse T cells. TCR stimulation promotes SLP-76-Ubc9 binding, accompanied by an increase in SLP-76 SUMOylation. Ubc9 binds to the extreme C terminus of SLP-76 spanning residues 516-533 and SUMOylates SLP-76 at two conserved residues K266 and K284. In addition, SLP-76 and Ubc9 synergizes to augment the TCR-mediated IL-2 transcription by NFAT in a manner dependent of SUMOylation of SLP-76. Moreover, although not affecting the TCR proximal signaling events, the Ubc9- mediated SUMOylation of SLP-76 is required for TCR-induced assembly of Ubc9-NFAT complex for IL-2 transcription. Together, these results suggest that Ubc9 modulates the function of SLP-76 in T cell activation both by direct interaction and by SUMOylation of SLP-76 and that the Ubc9-SLP-76 module acts as a novel regulatory complex in the control of T cell activation.
AB - Although the immune adaptor SH2 domain containing leukocyte phosphoprotein of 76 kDa (SLP-76) integrates and propagates the TCR signaling, the regulation of SLP-76 during the TCR signaling is incompletely studied. In this article, we report that SLP- 76 interacts with the small ubiquitin-like modifier (SUMO) E2 conjugase Ubc9 and is a substrate for Ubc9-mediated SUMOylation in human and mouse T cells. TCR stimulation promotes SLP-76-Ubc9 binding, accompanied by an increase in SLP-76 SUMOylation. Ubc9 binds to the extreme C terminus of SLP-76 spanning residues 516-533 and SUMOylates SLP-76 at two conserved residues K266 and K284. In addition, SLP-76 and Ubc9 synergizes to augment the TCR-mediated IL-2 transcription by NFAT in a manner dependent of SUMOylation of SLP-76. Moreover, although not affecting the TCR proximal signaling events, the Ubc9- mediated SUMOylation of SLP-76 is required for TCR-induced assembly of Ubc9-NFAT complex for IL-2 transcription. Together, these results suggest that Ubc9 modulates the function of SLP-76 in T cell activation both by direct interaction and by SUMOylation of SLP-76 and that the Ubc9-SLP-76 module acts as a novel regulatory complex in the control of T cell activation.
UR - http://www.scopus.com/inward/record.url?scp=85075223932&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1900556
DO - 10.4049/jimmunol.1900556
M3 - Article
C2 - 31666306
AN - SCOPUS:85075223932
SN - 0022-1767
VL - 203
SP - 3023
EP - 3036
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -