ZFYVE21 is a complement-induced Rab5 effector that activates non-canonical NF-κB via phosphoinosotide remodeling of endosomes

Fang, Caodi; Manes, Thomas D.; Liu, Lufang; Liu, Kevin; Qin, Lingfeng; Li, Guangxin; Tobiásová, Zuzana; Kirkiles-Smith, Nancy C.; Patel, Mitul K.; Merola, Jonathan; Fu, Whitney; Liu, Rebecca; Xie, Catherine; Tietjen, Gregory T.; Nigrović, Peter A.; Tellides, George; Pober, Jordan S.; Jane‐wit, Dan

doi:10.1038/s41467-019-10041-2

Cited by 32 publications

(59 citation statements)

References 38 publications

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“…Smurf2 belongs to the HECT family of E3 ubiquitinated ligases and was originally thought to play a crucial role in embryogenesis, adult tissue homeostasis and the pathogenesis of various human diseases . As E3 ubiquitination ligase Smurf2 has many binding substrates, such as TGF‐β receptor to regulate TGF‐β pathway, binding with PTEN to sequential recruitment of activated Akt and NF‐κB‐inducing kinase (NIK) and interacting with DNA topoisomerase IIα (Topo IIα) ensure genomic integrity and unaltered chromosome inheritance . However, there are few reports of the involvement of Smurf2 in cardiovascular diseases.…”

Section: Discussionmentioning

confidence: 99%

The E3 ubiquitin ligase Smurf2 regulates PARP1 stability to alleviate oxidative stress‐induced injury in human umbilical vein endothelial cells

Hao

Zhang

et al. 2020

J Cellular Molecular Medi

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Oxidative stress injury is involved in many cardiovascular diseases, like hypertension and myocardial infarction. Ubiquitination is a ubiquitous protein post-translational modification that controls a wide range of biological functions and plays a crucial role in maintaining the homeostasis of cells in physiology and disease. Many studies have shown that oxidative stress damage is inextricably linked to ubiquitination. We demonstrate that Smurf2, an E3 ubiquitinated ligase, is involved in HUVEC apoptosis induced by oxidative stress to alleviate H 2 O 2 -induced reactive oxygen species (ROS) production and the apoptosis of human umbilical vein endothelial cells (HUVECs).At the same time, we found that Smurf2 can bind the poly(ADP-ribose) polymerase-1(PARP1), and the interaction is enhanced under the stimulation of oxidative stress.We further study and prove that Smurf2 can promote PARP1 ubiquitination and degradation. Collectively, we demonstrate Smurf2 degradation of overactivated PARP1 by ubiquitin-proteasome pathway to protect HUVEC and alleviate oxidative stress injury. K E Y W O R D Sapoptosis, Smurf2, ubiquitination | 4601 QIAN et Al.

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Section: Discussionmentioning

confidence: 99%

The E3 ubiquitin ligase Smurf2 regulates PARP1 stability to alleviate oxidative stress‐induced injury in human umbilical vein endothelial cells

Hao

Zhang

et al. 2020

J Cellular Molecular Medi

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“…The active form of Rab5 is crucial for recruitment but not for the activation of AKT. 305 The formation of MAC + endosome, but not TRAFs-cIAPs is crucial to MAC-induced non-canonical NF-κB activation.…”

Section: Regulation Of Non-canonical Nf-κb Pathwaymentioning

confidence: 99%

Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study

Lin

Zhang

et al. 2020

Sig Transduct Target Ther

973

568

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NF-κB pathway consists of canonical and non-canonical pathways. The canonical NF-κB is activated by various stimuli, transducing a quick but transient transcriptional activity, to regulate the expression of various proinflammatory genes and also serve as the critical mediator for inflammatory response. Meanwhile, the activation of the non-canonical NF-κB pathway occurs through a handful of TNF receptor superfamily members. Since the activation of this pathway involves protein synthesis, the kinetics of non-canonical NF-κB activation is slow but persistent, in concordance with its biological functions in the development of immune cell and lymphoid organ, immune homeostasis and immune response. The activation of the canonical and non-canonical NF-κB pathway is tightly controlled, highlighting the vital roles of ubiquitination in these pathways. Emerging studies indicate that dysregulated NF-κB activity causes inflammation-related diseases as well as cancers, and NF-κB has been long proposed as the potential target for therapy of diseases. This review attempts to summarize our current knowledge and updates on the mechanisms of NF-κB pathway regulation and the potential therapeutic application of inhibition of NF-κB signaling in cancer and inflammatory diseases.

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“…e crucial effectors of Rab5 are early endosome antigen-1 (EEA1) [28,29], rabaptin-5 [30,31,37], rabenosyn-5 [32,38], APPL1/2 [33,34], and ZFYVE21 [35] ( Table 1).…”

Section: E Effectors Of Rab5mentioning

confidence: 99%

The Emerging Role of Rab5 in Membrane Receptor Trafficking and Signaling Pathways

Yuan

Song

2020

Biochemistry Research International

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Ras analog in brain (Rab) proteins are small guanosine triphosphatases (GTPases) that belong to the Ras-like GTPase superfamily, and they can regulate vesicle trafficking. Rab proteins alternate between an activated (GTP-bound) state and an inactivated (GDP-bound) state. Early endosome marker Rab5 GTPase, a key member of the Rab family, plays a crucial role in endocytosis and membrane transport. The activated-state Rab5 recruits its effectors and regulates the internalization and trafficking of membrane receptors by regulating vesicle fusion and receptor sorting in the early endosomes. In this review, we summarize the role of small Rab GTPases Rab5 in membrane receptor trafficking and the activation of signaling pathways, such as Ras/MAPK and PI3K/Akt, which ultimately affect cell growth, apoptosis, tumorigenesis, and tumor development. This review may provide some insights for our future research and novel therapeutic targets for diseases.

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ZFYVE21 is a complement-induced Rab5 effector that activates non-canonical NF-κB via phosphoinosotide remodeling of endosomes

Cited by 32 publications

References 38 publications

The E3 ubiquitin ligase Smurf2 regulates PARP1 stability to alleviate oxidative stress‐induced injury in human umbilical vein endothelial cells

The E3 ubiquitin ligase Smurf2 regulates PARP1 stability to alleviate oxidative stress‐induced injury in human umbilical vein endothelial cells

Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study

The Emerging Role of Rab5 in Membrane Receptor Trafficking and Signaling Pathways

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