SUMO‐specific protease 2 (SENP2) suppresses keratinocyte migration by targeting NDR1 for de‐SUMOylation

Xiao, Ning; Li, Hui; Yu, Wook-Joon; Li, Zhuoshi; Fang, Haiping; Peng, Yung-Hsing; Mao, He-shui; Fang, Yong; Ni, Wei; Yao, Min

doi:10.1096/fj.201800353r

Cited by 12 publications

(3 citation statements)

References 36 publications

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“…[ 38 ] Cell proliferation and migration ability were evaluated according to the reported procedures. [ 25c,39 ] The detailed procedures are provided in the Supporting Information.…”

Section: Methodsmentioning

confidence: 99%

Chiral Hydrogel Accelerates Re‐Epithelization in Chronic Wounds via Mechanoregulation

Zhu

Xing

Dou

et al. 2022

Adv Healthcare Materials

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Chronic wounds, such as diabetic foot ulcers (DFU), are a serious clinical problem. It is a challenge for the conventional wound dressings to achieve the desirable therapeutic efficacy due to the lack of biomimetic structural environment for rapid re-epithelization. Inspired by the naturally existing chiral structures in skin, a novel amino acid-based chiral hydrogel dressing is developed, consisting of left-handed or right-handed helical fibers self-assembled by l/d-phenylalanine derivatives. Compared to the levorotatory chiral hydrogel (LH), the dextral chiral hydrogel (DH) shows the ability to enhance cell adhesion, proliferation, and migration, and strongly promotes diabetic wound healing and re-epithelialization with a drug-free mode. Interestingly, the dextral chiral hydrogel is able to actively increase adsorption of type I collagen and promote proliferation and migration of keratinocyte in an integrin and YAP-mediated manner. This study not only provides a novel strategy for treatment of chronic wounds by utilizing dextral chiral hydrogel dressings, but also unveils the molecular mechanism for effect of dextral chiral structures on the promoted proliferation of keratinocyte.

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“…[ 38 ] Cell proliferation and migration ability were evaluated according to the reported procedures. [ 25c,39 ] The detailed procedures are provided in the Supporting Information.…”

Section: Methodsmentioning

confidence: 99%

Chiral Hydrogel Accelerates Re‐Epithelization in Chronic Wounds via Mechanoregulation

Zhu

Xing

Dou

et al. 2022

Adv Healthcare Materials

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“…PIPKIγi2 or PIPKIγi2‐K591R was subcloned into the pGEX vector with a GST tag by standard cloning methods. The SUMOylated PIPKIγ was purified according to the previous report . Briefly, we co‐transfected recombinant plasmids pGEX‐PIPKIγ (WT or K591R) with (or without) pE1E2S1 into Escherichia coli BL21 (DE3) competent cells.…”

Section: Methodsmentioning

confidence: 99%

SUMOylation is required for PIPK1γ‐driven keratinocyte migration and growth

Liu

Cai

et al. 2019

The FEBS Journal

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PIPKIγ, a key member of the type I phosphatidylinositol 4‐phosphate kinase (PIPKI) family that regulates the spatial‐temporal generation of PIP2, has been implicated in diverse biological processes including cell survival, cell polarity, and cell migration. An essential role of PIPKIγ in tumor cells and nerve cells has been established in previous studies. However, the function and regulatory mechanism of PIPKIγ remains incompletely understood. Here, we showed that PIPKIγ can specifically associate with the SUMO‐conjugating (E2) enzyme UBC9 and can be SUMOylated both in vivo and in vitro. We further identified that Lys‐591 is the critical SUMO‐acceptor site of PIPKIγ and that SUMO conjugation at this site is required for PIPKIγ‐driven keratinocyte migration and growth. Mechanistically, SUMOylation deficiency significantly disrupts PIPKIγ‐mediated generation of intracellular PIP2, rather than the subcellular translocation and protein stability of PIPKIγ. Our findings reveal that PIPKIγ is a novel SUMOylation target and highlight the essential role of PIPKIγ SUMOylation in human keratinocyte function, providing an important orientation for in‐depth study of wound repair.

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“…SENP2 upregulation in MCF7 breast cancer cells was led to reduced glycolysis, but SENP2 knockout in MEF cells resulted in enhanced glycolysis (Tang et al, 2013). SENP2 prevents keratinocyte migration by targeting NDR1 for deSUMOylation and inhibiting wound healing (Xiao et al, 2019). SUSP4 (mouse SENP2) overexpression repressed cell growth, but SUSP4 knockdown by RNA interference (RNAi) increased cell growth (Lee et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Identification of Natural Products as SENP2 Inhibitors for Targeted Therapy in Heart Failure

2022

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Aims: Sentrin-specific protease -2 (SENP2) is involved in deSUMOylation. Increased deSUMOylation in murine hearts by SENP2 upregulation resulted in cardiac dysfunction and congenital heart defects. Natural compounds via regulating cell proliferation and survival, induce cell cycle cessation, cell death, apoptosis, and producing reactive oxygen species and various enzyme systems cause disease prevention. Then, natural compounds can be suitable inhibitors and since SENP2 is a protein involved in heart disease, so our aim was inhibition of SENP2 by natural products for heart disease treatment. Material and methods: Molecular docking and molecular dynamics simulation of natural products i.e. Gallic acid (GA), Caffeic acid (CA), Thymoquinone (TQ), Betanin, Betanidin, Fisetin, and Ebselen were done to evaluate the SENP2 inhibitory effect of these natural products. The toxicity of compounds was also predicted. Results: The results showed that Betanin constituted a stable complex with SENP2 active site as it revealed low RMSD, high binding energy, and hydrogen bonds. Further, as compared to Ebselen, Betanin demonstrated low toxicity, formed a stable complex with SENP2 via four to seven hydrogen bonds, and constituted more stable MD plots. Therefore, depending upon the outcomes presented herein, Betanin significantly inhibited SENP2 and hence may be considered as a suitable natural compound for the treatment of heart failure. Further clinical trials must be conducted to validate its use as a potential SENP2 inhibitor.

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SUMO‐specific protease 2 (SENP2) suppresses keratinocyte migration by targeting NDR1 for de‐SUMOylation

Cited by 12 publications

References 36 publications

Chiral Hydrogel Accelerates Re‐Epithelization in Chronic Wounds via Mechanoregulation

Chiral Hydrogel Accelerates Re‐Epithelization in Chronic Wounds via Mechanoregulation

SUMOylation is required for PIPK1γ‐driven keratinocyte migration and growth

Identification of Natural Products as SENP2 Inhibitors for Targeted Therapy in Heart Failure

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