SUMO‐specific protease 2 (SENP2) suppresses keratinocyte migration by targeting NDR1 for de‐SUMOylation. Issue 1 (3rd July 2018)

• Record Type: Journal Article
• Authors: Xiao, Ning; Li, Hui; Yu, Weirong; Gu, Chuan; Fang, Houshun; Peng, Yinbo; Mao, Heshui; Fang, Yong; Ni, Wei; Yao, Min
• Is Part Of: FASEB journal. Volume 33:Issue 1(2019)
• Page Start: 163
• Page End: 174
• Publication Date: 2018-07-03
• Subjects: STK38 -- LLL -- MAPK activation; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201800353R
• Languages: English
• ISSNs: 0892-6638

Abstract

ABSTRACT: A key member of the sentrin/small ubiquitin‐like modifier (SUMO)‐specific protease (SENP) family, SENP2 has been shown to implicate embryonic development, fatty acid metabolism, atherosclerosis, and neurodegenerative diseases. However, other biologic functions of SENP2 and its specific targets are incompletely understood. Here, we uncovered a novel role of SENP2 in negative regulation of keratinocyte migration, a process crucial to wound epithelialization. Defects in this function are often associated with the clinical phenotypes of chronic nonhealing wounds. Mechanistically, SENP2 as a specific de‐SUMOylase targets NDR1 (nuclear Dbf2‐related 1), also called STK38 (serine‐threonine kinase 38), for de‐SUMOylation and SUMO conjugation of NDR1 on Lys‐465 attenuates its inhibition of p38/ERK1/2 activation by decreasing the association of NDR1 with MEK kinase 1/2. Significantly, low‐level laser (LLL) irradiation increases NDR1 SUMOylation and subsequent p38/ERK1/2 activation via down‐regulation of SENP2, leading to faster keratinocyte migration. Our findings fill the gaps that linger in the basic mechanisms underlying LLL therapy.—Xiao, N., Li, H., Yu, W., Gu, C., Fang, H., Peng, Y., Mao, H., Fang, Y., Ni, W., Yao, M.SUMO‐specific protease 2 (SENP2) suppresses keratinocyte migration by targeting NDR1 for de‐SUMOylation. FASEB J. 33, 163–174 (2019). www.fasebj.org