4.8 Article

Regulation of WASH-Dependent Actin Polymerization and Protein Trafficking by Ubiquitination

期刊

CELL
卷 152, 期 5, 页码 1051-1064

出版社

CELL PRESS
DOI: 10.1016/j.cell.2013.01.051

关键词

-

资金

  1. Cancer Prevention and Research Initiative of Texas [R1117]
  2. Department of Defense [CA110261]
  3. Howard Hughes Medical Institute
  4. Mayo Foundation
  5. Michael L. Rosenberg Scholar in Medical Research fund
  6. NIH [R01-AI065474, R01-GM063692, R01-GM56322]
  7. Sara and Frank McKnight Fellowship
  8. Welch Foundation [I-1544, I-1389]

向作者/读者索取更多资源

Endosomal protein trafficking is an essential cellular process that is deregulated in several diseases and targeted by pathogens. Here, we describe a role for ubiquitination in this process. We find that the E3 RING ubiquitin ligase, MAGE-L2-TRIM27, localizes to endosomes through interactions with the retromer complex. Knockdown of MAGE-L2-TRIM27 or the Ube2O E2 ubiquitin-conjugating enzyme significantly impaired retromer-mediated transport. We further demonstrate that MAGE-L2-TRIM27 ubiquitin ligase activity is required for nucleation of endosomal F-actin by the WASH regulatory complex, a known regulator of retromer-mediated transport. Mechanistic studies showed that MAGE-L2-TRIM27 facilitates K63-linked ubiquitination of WASH K220. Significantly, disruption of WASH ubiquitination impaired endosomal F-actin nucleation and retromer-dependent transport. These findings provide a cellular and molecular function for MAGE-L2-TRIM27 in retrograde transport, including an unappreciated role of K63-linked ubiquitination and identification of an activating signal of the WASH regulatory complex.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Cell Biology

Phosphorylation of SNX27 by MAPK11/14 links cellular stress-signaling pathways with endocytic recycling

Lejiao Mao, Chenyi Liao, Jiao Qin, Yanqiu Gong, Yifei Zhou, Shasha Li, Zhe Liu, Huaqing Deng, Wankun Deng, Qingxiang Sun, Xianming Mo, Yu Xue, Daniel D. Billadeau, Lunzhi Dai, Guohui Li, Da Jia

Summary: This study reveals that external stimuli such as starvation, LPS, and inflammatory cytokines can inhibit endocytic recycling of proteins by activating MAPK11/14, leading to a disruption in the balance between recycling and degradation. Stress-induced kinases phosphorylate SNX27 at Ser51, altering its binding with cargo proteins and thereby suppressing endocytic recycling. The findings suggest that cells can modulate endocytic recycling in response to stress signals, providing new insights into how cells cope with stress and conserve energy.

JOURNAL OF CELL BIOLOGY (2021)

Article Multidisciplinary Sciences

Phosphorylation and chromatin tethering prevent cGAS activation during mitosis

Tuo Li, Tuozhi Huang, Mingjian Du, Xiang Chen, Fenghe Du, Junyao Ren, Zhijian J. Chen

Summary: The study found that cGAS activity is selectively suppressed during mitosis in human cell lines due to hyperphosphorylation at the N terminus by mitotic kinases and prevention of oligomerization of chromatin-bound cGAS, ensuring its inactivity during mitosis when associated with chromatin.

SCIENCE (2021)

Review Cell Biology

Targeting Endosomal Recycling Pathways by Bacterial and Viral Pathogens

Xin Yong, Lejiao Mao, Xiaofei Shen, Zhen Zhang, Daniel D. Billadeau, Da Jia

Summary: Endosomes are crucial cellular stations for protein trafficking, where proteins can be degraded or recycled to different cellular destinations. Recent studies have shown that pathogens like bacteria and viruses exploit host endosomal recycling pathways for their survival and replication. This manipulation of host signaling pathways by pathogens deepens our understanding of the molecular intricacies regulating endosomal trafficking.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

Article Nanoscience & Nanotechnology

Cancer Therapy with Nanoparticle-Medicated Intracellular Expression of Peptide CRM1-Inhibitor

Min Sui, Meimei Xiong, Yuling Li, Qiao Zhou, Xiaofei Shen, Da Jia, Maling Gou, Qingxiang Sun

Summary: Peptides can be designed as non-covalent inhibitors for molecularly targeted therapy, and nanoparticle-mediated gene expression systems can efficiently deliver peptides into cancer cells for improved therapeutic efficacy. This method showed effectiveness against cancer cells in experiments and may provide a new approach for the development of targeted therapy in the future.

INTERNATIONAL JOURNAL OF NANOMEDICINE (2021)

Article Chemistry, Medicinal

Structure-Guided Design of the First Noncovalent Small-Molecule Inhibitor of CRM1

Yuqin Lei, Qi An, Xiao-Fei Shen, Min Sui, Chungen Li, Da Jia, Youfu Luo, Qingxiang Sun

Summary: The research team successfully designed a noncovalent CRM1 inhibitor with high affinity for human and yeast CRM1 through crystal structure studies, showing superior properties compared to covalent inhibitors. This discovery opens up new avenues for the development of more effective, less toxic, and broad-spectrum anticancer/antiviral therapies.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Plant Sciences

Novel Mechanistic Observations and NES-Binding Groove Features Revealed by the CRM1 Inhibitors Plumbagin and Oridonin

Yuqin Lei, Yuling Li, Yuping Tan, Zhiyong Qian, Qiao Zhou, Da Jia, Qingxiang Sun

Summary: Plant-derived CRM1 inhibitors plumbagin and oridonin inhibit CRM1 activity through multiple mechanisms, including directly targeting the NES groove and promoting CRM1 aggregation. The oridonin complex reveals for the first time a more open NES groove structure. These findings may provide new strategies for the development of CRM1 inhibitors.

JOURNAL OF NATURAL PRODUCTS (2021)

Article Biochemistry & Molecular Biology

Cryo-EM structures of human GMPPA-GMPPB complex reveal how cells maintain GDP-mannose homeostasis

Lvqin Zheng, Zhe Liu, Yan Wang, Fan Yang, Jinrui Wang, Wenjie Huang, Jiao Qin, Min Tian, Xiaotang Cai, Xiaohui Liu, Xianming Mo, Ning Gao, Da Jia

Summary: The structural elucidation and functional analysis of the human GMPPA-GMPPB complex demonstrates how GMPPA acts as a 'sensor' to regulate GMPPB activity and maintain cellular GDP-mannose homeostasis through allosteric mechanisms. This study reveals that GMPPA has a higher affinity to GDP-mannose compared to GMPPB, and can inhibit the catalytic activity of GMPPB. Disruption of GMPPA-GMPPB interactions or GDP-mannose binding to GMPPA leads to abnormal development phenotypes in zebrafish, similar to individuals with GMPPA or GMPPB mutations.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2021)

Article Multidisciplinary Sciences

TBK1 recruitment to STING activates both IRF3 and NF-κB that mediate immune defense against tumors and viral infections

Seoyun Yum, Minghao Li, Yan Fang, Zhijian J. Chen

Summary: This study shows that STING can function independently of type I interferons and autophagy, and that TBK1 recruitment to STING is essential for antiviral and antitumor immunity.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

Editorial Material Cell Biology

iCAL: a new pipeline to investigate autophagy selectivity and cancer

Weizhi Zhang, Zhu Han, Yu Xue, Da Jia

Summary: Macroautophagy/autophagy can selectively degrade misfolded proteins and damaged organelles, potentially contributing to cancer. Mutations in proteins like ATG4B, STBD1, EHMT2, and BRAF disrupt their interactions with LC3 and autophagy activities. The poorly-characterized protein STBD1 inhibits tumor growth through metabolism reprogramming and a patient-derived mutation in STBD1 promotes tumor growth by disrupting the interaction with LC3.

AUTOPHAGY (2021)

Article Biochemistry & Molecular Biology

Biophysical and biochemical properties of PHGDH revealed by studies on PHGDH inhibitors

Yuping Tan, Xia Zhou, Yanqiu Gong, Kun Gou, Youfu Luo, Da Jia, Lunzhi Dai, Yinglan Zhao, Qingxiang Sun

Summary: The study identified a new PHGDH inhibitor, oridonin, and revealed the mechanism of its binding to PHGDH structure, providing new insights for the future design of PHGDH inhibitors.

CELLULAR AND MOLECULAR LIFE SCIENCES (2022)

Article Immunology

TBK1 recruitment to STING mediates autoinflammatory arthritis caused by defective DNA clearance

Tong Li, Seoyun Yum, Minghao Li, Xiang Chen, Xiaoxia Zuo, Zhijian J. Chen

Summary: Defective DNA clearance in DNase II-/- mice leads to lethal inflammatory diseases that can be rescued by deleting cGAS or STING. The study found that distinct signaling pathways downstream of STING play different roles in disease manifestation, with TBK1 recruitment to STING mediating autoinflammatory arthritis caused by DNase II deficiency. This discovery may provide new insights into therapeutic strategies for certain autoinflammatory diseases.

JOURNAL OF EXPERIMENTAL MEDICINE (2021)

Review Biochemistry & Molecular Biology

Role of Seipin in Human Diseases and Experimental Animal Models

Yuying Li, Xinmin Yang, Linrui Peng, Qing Xia, Yuwei Zhang, Wei Huang, Tingting Liu, Da Jia

Summary: This study comprehensively summarizes the phenotypes, mechanisms, and treatment options of human diseases caused by BSCL2 gene mutations, as well as relevant findings in animal studies. Restoring adipose tissue function and targeting seipin-related pathways are effective strategies for CGL2 treatment and also have potential therapeutic value in other diseases.

BIOMOLECULES (2022)

Review Biochemistry & Molecular Biology

Protein-protein interfaces in molecular glue-induced ternary complexes: classification, characterization, and prediction

Huan Rui, Kate S. Ashton, Jaeki Min, Connie Wang, Patrick Ryan Potts

Summary: Molecular glues are small molecules that stabilize protein-protein interactions and have promising therapeutic potential. Clinical compounds called molecular glue degraders can stabilize interactions between E3 ubiquitin ligases and target proteins, leading to targeted protein degradation. However, the rational discovery of molecular glues is challenging due to limited understanding of the interactions they stabilize. This review summarizes the structures and interface properties of known molecular glue-induced ternary complexes and discusses computational approaches for predicting protein-protein interfaces, providing valuable insights for future rational molecular glue discovery.

RSC CHEMICAL BIOLOGY (2023)

Article Multidisciplinary Sciences

Ubiquitin-like conjugation by bacterial cGAS enhances anti-phage defence

Justin M. Jenson, Tuo Li, Fenghe Du, Chee-Kwee Ea, Zhijian J. Chen

Summary: cGAS is a conserved enzyme that plays a crucial role in immune defense. It is activated by DNA to produce cGAMP, which leads to the expression of antimicrobial genes. In bacteria, a similar enzyme system called CBASS has been discovered, where a protein called Cap2 forms a thioester bond with cGAS and promotes its conjugation to target proteins, increasing cGAMP production.

NATURE (2023)

Review Chemistry, Multidisciplinary

Target and tissue selectivity of PROTAC degraders

Robert G. Guenette, Seung Wook Yang, Jaeki Min, Baikang Pei, Patrick Ryan Potts

Summary: Targeted protein degradation strategies, such as PROTAC and molecular glue technology, have provided highly selective control of target inhibition, revolutionizing the approach to challenging protein targets. These advancements have broad implications in treating diseases by expanding the range of possible targets that can be addressed by small molecules.

CHEMICAL SOCIETY REVIEWS (2022)

暂无数据