Cul3-KLHL20 E3 ubiquitin ligase plays a key role in the arms race between HIV-1 Nef and host SERINC5 restriction

Li, Sunan; Li, Rongrong; Ahmad, Iqbal; Liu, Xiaomeng; Johnson, Silas F.; Sun, Liangliang; Zheng, Yong Hui

doi:10.1038/s41467-022-30026-y

Cited by 10 publications

(5 citation statements)

References 39 publications

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“…The ubiquitination system is large and complex. One or more E3 ligases may act on the substrate, resulting in different topologies, such as K11/K48, K63/M1, K29/K48, K33/K48, etc., and determining the fate of the substrate in a variety of ways (Emmerich et al, 2013; Kaiho‐Soma et al, 2021; Li et al, 2022; Rana et al, 2017; Yau et al, 2017). Our results also confirmed that there were more than one ubiquitin‐linked chains for MrgC.…”

Section: Discussionmentioning

confidence: 99%

USP48 alleviates bone cancer pain and regulates MrgC stabilization in spinal cord neurons of male mice

Hou

Huang

et al. 2023

European Journal of Pain

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Bone cancer pain (BCP), as a common type of cancer pain, is a specific pain state that differs from inflammatory pain and neuropathic pain (Gadepalli et al., 2021). BCP brings a series of adverse effects, including nausea and vomiting, loss of appetite, anxiety, depression, fear and helplessness, which make the patients suffer (Sung et al., 2021). With advances in medical technology, most patients with malignancies have significantly longer survival (Sung et al., 2021). However, the bone disease and pain associated with metastatic cancer has yet to be addressed. The development of new therapeutic approaches and drug targets for BCP is, therefore, particularly urgent.Mas-related G protein-coupled receptor C (MrgC) is a member of the Mrg receptor family that are expressed in small-diameter primary sensory neurons. The activation of MrgC can inhibit a variety of pains including inflammatory pain, neuropathic pain and BCP (He et al., 2014;Jiang et al., 2013;Sun, Zhang, et al., 2016). Our previous studies have shown that MrgC plays an important role in the development of BCP, and can inhibit Ca2+ inward

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Section: Discussionmentioning

confidence: 99%

USP48 alleviates bone cancer pain and regulates MrgC stabilization in spinal cord neurons of male mice

Hou

Huang

et al. 2023

European Journal of Pain

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“…This results in the phosphorylation of serine 360 in S5’s ICL4 and the subsequent AP-2-dependent internalization of S5 in Rab7+ endosomes and lysosomal degradation. A recent study by Li and colleagues [ 78 ] identified the ubiquitination of lysine 130 in S5 caused by the E3 ubiquitin ligase Cul3-KLHL20 as an important regulator of both its targeting to the plasma membrane and its internalization and degradation. While K33-linked ubiquitination is involved in the plasma membrane targeting of S5, the K48-linked ubiquitination of S5 facilitates its internalization and, thus, Nef-mediated antagonism.…”

Section: Mechanism Of Nef-mediated Antagonism Of S5 Restriction Of Hi...mentioning

confidence: 99%

Beyond Impairment of Virion Infectivity: New Activities of the Anti-HIV Host Cell Factor SERINC5

Sid Ahmed,

Bajak,

Fackler

2024

Viruses

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Members of the serine incorporator (SERINC) protein family exert broad antiviral activity, and many viruses encode SERINC antagonists to circumvent these restrictions. Significant new insight was recently gained into the mechanisms that mediate restriction and antagonism. In this review, we summarize our current understanding of the mode of action and relevance of SERINC proteins in HIV-1 infection. Particular focus will be placed on recent findings that provided important new mechanistic insights into the restriction of HIV-1 virion infectivity, including the discovery of SERINC’s lipid scramblase activity and its antagonism by the HIV-1 pathogenesis factor Nef. We also discuss the identification and implications of several additional antiviral activities by which SERINC proteins enhance pro-inflammatory signaling and reduce viral gene expression in myeloid cells. SERINC proteins emerge as versatile and multifunctional regulators of cell-intrinsic immunity against HIV-1 infection.

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“…Non-proteolytic roles for E3 ligases, where ubiquitination induces changes in protein-protein interaction networks at the Golgi were reported to regulate membrane trafficking. A CRL consisting of CUL3 and the KLHL20 substrate receptor localizes to the TGN and assembles K33-linked poly-Ub chains on its substrates ( Yuan et al, 2014 ; Li et al, 2022 ). Poly-ubiquitination of the substrate Crn7 promotes Crn7 localization at the TGN, where it exerts its F-actin stabilizing activity to support transport carrier formation ( Yuan et al, 2014 ).…”

Section: Soluble E3 Ligases Are Recruited To Golgi Substrate Proteinsmentioning

confidence: 99%

“…Disruption of this pathway leads to a block in basal secretory trafficking ( Yuan et al, 2014 ). Poly-ubiquitination of Serinc5, an integral membrane protein, by CUL3-KLHL20 at the TGN promotes Serinc5 trafficking to the PM and thereby regulates its antiviral activity ( Li et al, 2022 ). At the PM, Sercin5 is incorporated into HIV-1 viral particles and reduces their infectivity ( Li et al, 2022 ).…”

Section: Soluble E3 Ligases Are Recruited To Golgi Substrate Proteinsmentioning

confidence: 99%

“…Poly-ubiquitination of Serinc5, an integral membrane protein, by CUL3-KLHL20 at the TGN promotes Serinc5 trafficking to the PM and thereby regulates its antiviral activity ( Li et al, 2022 ). At the PM, Sercin5 is incorporated into HIV-1 viral particles and reduces their infectivity ( Li et al, 2022 ). Golgi-related transport is also activated by phosphorylation, specifically by the tyrosine kinase Src ( Pulvirenti et al, 2008 ).…”

Section: Soluble E3 Ligases Are Recruited To Golgi Substrate Proteinsmentioning

confidence: 99%

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Ubiquitin-mediated degradation at the Golgi apparatus

Buzuk

Hellerschmied

2023

Front. Mol. Biosci.

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The Golgi apparatus is an essential organelle of the secretory pathway in eukaryotic cells. It processes secretory and transmembrane proteins and orchestrates their transport to other endomembrane compartments or the plasma membrane. The Golgi apparatus thereby shapes the cell surface, controlling cell polarity, cell-cell communication, and immune signaling. The cytosolic face of the Golgi hosts and regulates signaling cascades, impacting most notably the DNA damage response and mitosis. These essential functions strongly depend on Golgi protein homeostasis and Golgi integrity. Golgi fragmentation and consequent malfunction is associated with neurodegenerative diseases and certain cancer types. Recent studies provide first insight into the critical role of ubiquitin signaling in maintaining Golgi integrity and in Golgi protein quality control. Similar to well described pathways at the endoplasmic reticulum, ubiquitin-dependent degradation of non-native proteins prevents the accumulation of toxic protein aggregates at the Golgi. Moreover, ubiquitination regulates Golgi structural rearrangements in response to cellular stress. Advances in elucidating ubiquitination and degradation events at the Golgi are starting to paint a picture of the molecular machinery underlying Golgi (protein) homeostasis.

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Cul3-KLHL20 E3 ubiquitin ligase plays a key role in the arms race between HIV-1 Nef and host SERINC5 restriction

Cited by 10 publications

References 39 publications

USP48 alleviates bone cancer pain and regulates MrgC stabilization in spinal cord neurons of male mice

USP48 alleviates bone cancer pain and regulates MrgC stabilization in spinal cord neurons of male mice

Beyond Impairment of Virion Infectivity: New Activities of the Anti-HIV Host Cell Factor SERINC5

Ubiquitin-mediated degradation at the Golgi apparatus

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