2. Academic Validation
  3. TRIM31 facilitates K27-linked polyubiquitination of SYK to regulate antifungal immunity

TRIM31 facilitates K27-linked polyubiquitination of SYK to regulate antifungal immunity

  • Signal Transduct Target Ther. 2021 Aug 6;6(1):298. doi: 10.1038/s41392-021-00711-3.
Xueer Wang  # 1,  Honghai Zhang  # 1,  Zhugui Shao 1,  Wanxin Zhuang 1,  Chao Sui 1,  Feng Liu 1,  Xiaorong Chen 1,  Jinxiu Hou 1,  Lingli Kong 1,  Hansen Liu 1,  Yi Zheng 1,  Bingyu Liu 1,  Tian Chen 2,  Lei Zhang 1,  Xinming Jia 3,  Chengjiang Gao 4
Affiliations

Affiliations

  • 1 Shandong Provincial Key Laboratory of Infection and Immunity & Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong, China.
  • 2 Department of Pathogenic Biology, School of Biomedical Sciences, Shandong University, Jinan, Shandong, China.
  • 3 Clinical Medicine Scientific and Technical Innovation Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
  • 4 Shandong Provincial Key Laboratory of Infection and Immunity & Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong, China. cgao@sdu.edu.cn.
  • # Contributed equally.
PMID: 34362877 DOI: 10.1038/s41392-021-00711-3
Abstract

Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase, which plays an essential role in both innate and adaptive immunity. However, the key molecular mechanisms that regulate Syk activity are poorly understood. Here we identified the E3 Ligase TRIM31 as a crucial regulator of Syk activation. We found that TRIM31 interacted with Syk and catalyzed K27-linked polyubiquitination at Lys375 and Lys517 of Syk. This K27-linked polyubiquitination of Syk promoted its plasma membrane translocation and binding with the C-type Lectin Receptors (CLRs), and also prevented the interaction with the Phosphatase SHP-1. Therefore, deficiency of Trim31 in bone marrow-derived dendritic cells (BMDCs) and macrophages (BMDMs) dampened SYK-mediated signaling and inhibited the secretion of proinflammatory cytokines and chemokines against the Fungal pathogen Candida albicans Infection. Trim31-/- mice were also more sensitive to C. albicans systemic Infection than Trim31+/+ mice and exhibited reduced Th1 and Th17 responses. Overall, our study uncovered the pivotal role of TRIM31-mediated K27-linked polyubiquitination on Syk activation and highlighted the significance of TRIM31 in anti-C. albicans immunity.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z