title: SUMOylation of PES1 upregulates its stability and function via inhibiting its ubiquitination.
abstract: PES1 is a component of the PeBoW complex, which is required for the maturation of 28S and 5.8S ribosomal RNAs, as well as for the formation of the 60S ribosome. Deregulation of ribosomal biogenesis can contribute to carcinogenesis. In this study, we showed that PES1 could be modified by the small ubiquitin-like modifier (SUMO) SUMO-1, SUMO-2 and SUMO-3, and SUMOylation of PES1 was stimulated by estrogen (E2). One major SUMOylation site (K517) was identified in the C-terminal Glu-rich domain of PES1. Substitution of K517 with arginine abolished the SUMOylation of PES1. SUMOylation also stabilized PES1 through inhibiting its ubiquitination. In addition, PES1 SUMOylation positively regulated the estrogen signaling pathway. SUMOylation enhanced the ability of PES1 to promote estrogen receptor α (ERα)-mediated transcription by increasing the stability of ERα, both in the presence and absence of E2. Moreover, SUMOylation of PES1 also increased the proportion of S-phase cells in the cell cycle and promoted the proliferation of breast cancer cells both in vitro and in vivo. These findings showed that posttranslational modification of PES1 by SUMOylation may serve as a key factor that regulates the function of PES1 in vivo.
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China.
authors.forename: Shujing
authors.initials: S
authors.lastname: Li
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Life Science and Medicine, Dalian University of Technology, Panjin, China.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Qu
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China.
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Xu
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Life Science and Medicine, Dalian University of Technology, Panjin, China.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Su
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China.|School of Life Science and Medicine, Dalian University of Technology, Panjin, China.
authors.forename: Huijian
authors.initials: H
authors.lastname: Wu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D019556:COS Cells; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D047628:Estrogen Receptor alpha; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*; D012339:RNA, Ribosomal, 28S / Q000378:metabolism; D012340:RNA, Ribosomal, 5.8S / Q000378:metabolism; D016601:RNA-Binding Proteins; D058207:Sumoylation; D015533:Transcriptional Activation; D054875:Ubiquitination
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C484463:PES1 protein, human; D011506:Proteins; D012339:RNA, Ribosomal, 28S; D012340:RNA, Ribosomal, 5.8S; D016601:RNA-Binding Proteins; D046988:Proteasome Endopeptidase Complex
keywords: PES1; SUMOylation; breast cancer; ubiquitination