SUMO‐specific protease 2 (SENP2) suppresses keratinocyte migration by targeting NDR1 for de‐SUMOylation
SUMO‐specific protease 2 (SENP2) suppresses keratinocyte migration by targeting NDR1 for de‐SUMOylation
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DOI：
10.1096/fj.201800353r
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发表时间：
2018-07
期刊：
影响因子：
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通讯作者：
N. Xiao;Hui Li;Wei-rong Yu;Chuan Gu;Houshun Fang;Yinbo Peng;Heshui Mao;Yong Fang;W. Ni;M. Yao
中科院分区：
文献类型：
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作者：
N. Xiao;Hui Li;Wei-rong Yu;Chuan Gu;Houshun Fang;Yinbo Peng;Heshui Mao;Yong Fang;W. Ni;M. Yao
SENP 2是sentrin/小泛素样修饰物（SUMO）特异性蛋白酶（SENP）家族的关键成员，已被证明与胚胎发育，脂肪酸代谢，动脉粥样硬化和神经退行性疾病有关。然而，SENP 2的其他生物学功能及其特异性靶点尚未完全了解。在这里，我们发现了SENP 2在角质形成细胞迁移的负调节中的新作用，角质形成细胞迁移是伤口上皮形成的关键过程。这种功能的缺陷通常与慢性不愈合伤口的临床表型有关。从机制上讲，SENP 2作为一种特异性去SUMO化酶，靶向NDR 1（核Dbf 2相关1），也称为STK 38（丝氨酸-苏氨酸激酶38），用于去SUMO化，并通过减少NDR 1与MEK激酶1/2的结合，使NDR 1在Lys-465上的SUMO缀合减弱其对p38/ERK 1/2活化的抑制。值得注意的是，低强度激光（LLL）照射通过下调SENP 2增加NDR 1 SUMO化和随后的p38/ERK 1/2激活，导致角质形成细胞迁移更快。我们的发现填补了LLL治疗基本机制中的空白。Xiao，N.，美国，Li，H.，余伟，古，C.，Fang，H.，中国农业科学院，彭，Y.，毛，H.，Fang，Y.，中国科学院，Ni，W.，Yao，M.SUMO特异性蛋白酶2（SENP 2）通过靶向NDR 1进行去SUMO化来抑制角质形成细胞迁移。FASEB J. 33，163-174（2019）。www.fasebj.org
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