LC Domain-Mediated Coalescence Is Essential for Otu Enzymatic Activity to Extend Drosophila Lifespan

Ji, Shanming; Luo, Yuewan; Cai, Qingshuang; Cao, Zhi-Jie; Zhao, Yuanyuan; Mei, Jie; Li, Chenxiao; Xia, Pengyan; Xie, Zhongwen; Xia, Zongping; Zhang, Jian; Sun, Qing; Chen, Dahua

doi:10.1016/j.molcel.2019.02.004

Cited by 36 publications

(43 citation statements)

References 46 publications

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“…Ji et al reveal that RNA plays an active in OTU enzymatic activity as a positive regulator. They reveal that the binding of RNA promotes the formation of OTU granules, highlighting the important regulatory and functional roles of RNA in OTU activity [176]. Another problem is our limited understanding of some OTUs, such as OTUD7A.…”

Section: Outlook and Discussionmentioning

confidence: 99%

The function and regulation of OTU deubiquitinases

Sui

et al. 2019

Front. Med.

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Post-translational modification of cellular proteins by ubiquitin regulates numerous cellular processes, including cell division, immune responses, and apoptosis. Ubiquitin-mediated control over these processes can be reversed by deubiquitinases (DUBs), which remove ubiquitin from target proteins and depolymerize polyubiquitin chains. Recently, much progress has been made in the DUBs. In humans, the ovarian tumor protease (OTU) subfamily of DUBs includes 16 members, most of which mediate cell signaling cascades. These OTUs show great variation in structure and function, which display a series of mechanistic features. In this review, we provide a comprehensive analysis of current progress in character, structure and function of OTUs, such as the substrate specificity and catalytic activity regulation. Then we discuss the relationship between some diseases and OTUs. Finally, we summarize the structure of viral OTUs and their function in immune escape and viral survival. Despite the challenges, OTUs might provide new therapeutic targets, due to their involvement in key regulatory processes.

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Section: Outlook and Discussionmentioning

confidence: 99%

The function and regulation of OTU deubiquitinases

Sui

et al. 2019

Front. Med.

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“…These proteins also harbor LC domains and are prone to self-assembly, raising the question as to whether these self-assembly properties are somehow linked to their enzymatic activity in addition to their binding to RNA. In this issue of Molecular Cell, Ji et al (2019) show that this is the case for the Drosophila RNA binding protein Otu (ovarian tumor). Otu is a deubiquitinase whose activity has been shown to regulate germline stem cell differentiation (Ji et al, 2017).…”

mentioning

confidence: 97%

“…The formation of amyloid fibers is usually associated with aging and neurodegeneration. In this issue of Molecular Cell, Ji et al (2019) demonstrate that the deubiquitinase Otu coalesces into amyloid-like fibers to enhance its activity and ensure its optimum biological function.…”

mentioning

confidence: 98%

“…The first part of the article by Ji et al (2019) is dedicated to show that Otu protein phase separates into solid (not liquid) amyloid fibers, both in vitro from purified protein and in vivo upon overexpression in Hek293 cells. The formation of Otu fibers depends on RNAs and strictly depends on the presence of the LC domain.…”

mentioning

confidence: 99%

“…The last part of the article by Ji et al (2019) investigates how Otu and Bam coalescence mediates their protecting effect in the gut, hence ensuring wildtype longevity. dTraf6 (Drosophila TNFreceptor-associated factor 6) is found to form a ternary complex with Otu and Bam.…”

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confidence: 99%

See 2 more Smart Citations

The Upper Hand of the Otu Amyloid Fibers: Increasing Enzymatic Activity and Prolonging Lifespan

Rabouille

2019

Molecular Cell

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14-3-3 Proteins are Potential Regulators of Liquid–Liquid Phase Separation

Huang

Zheng

et al. 2022

Cell Biochem Biophys

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The 14-3-3 family proteins are vital scaffold proteins that ubiquitously expressed in various tissues. They interact with numerous protein targets and mediate many cellular signaling pathways. The 14-3-3 binding motifs are often embedded in intrinsically disordered regions which are closely associated with liquid-liquid phase separation (LLPS). In the past ten years, LLPS has been observed for a variety of proteins and biological processes, indicating that LLPS plays a fundamental role in the formation of membraneless organelles and cellular condensates. While extensive investigations have been performed on 14-3-3 proteins, its involvement in LLPS is overlooked. To date, 14-3-3 proteins have not been reported to undergo LLPS alone or regulate LLPS of their binding partners. To reveal the potential involvement of 14-3-3 proteins in LLPS, in this review, we summarized the LLPS propensity of 14-3-3 binding partners and found that about one half of them may undergo LLPS spontaneously. We further analyzed the phase separation behavior of representative 14-3-3 binders and discussed how 14-3-3 proteins may be involved. By modulating the conformation and valence of interactions and recruiting other molecules, we speculate that 14-3-3 proteins can efficiently regulate the functions of their targets in the context of LLPS. Considering the critical roles of 14-3-3 proteins, there is an urgent need for investigating the involvement of 14-3-3 proteins in the phase separation process of their targets and the underling mechanisms.

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LC Domain-Mediated Coalescence Is Essential for Otu Enzymatic Activity to Extend Drosophila Lifespan

Cited by 36 publications

References 46 publications

The function and regulation of OTU deubiquitinases

The function and regulation of OTU deubiquitinases

The Upper Hand of the Otu Amyloid Fibers: Increasing Enzymatic Activity and Prolonging Lifespan

14-3-3 Proteins are Potential Regulators of Liquid–Liquid Phase Separation

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