title: OTUB1-catalyzed deubiquitination of FOXM1 facilitates tumor progression and predicts a poor prognosis in ovarian cancer.
abstract: Ubiquitination is essential for regulation of cell physiology, protein stability, and signal transduction [1]. Its dysregulation is an important factor in many diseases, including cancer. We explored the potential OTUB1-catalyzed deubiquitination of FOXM1, a transcription factor linked to carcinogenesis, and the biological consequence of that interaction in ovarian cancer. We found that FOXM1 is ubiquitinated by multiple polyUb chains and targeted for proteosomal degradation in a reaction dependent on its ubiquitination-required KEN box. Additionally, the OTUB1 N-terminus and catalytic triad bind to FOXM1, specifically catalyzing cleavage of the K48-specific ubiquitin linkage from FOXM1. Moreover, OTUB1-FOXM1 interaction drives tumor progression and OTUB1 expression predicts a poor prognosis in ovarian cancer. Our study suggests that inhibiting OTUB1-FOXM1 interaction is a potential new avenue for ovarian cancer therapy.
authors.affiliation: Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200044, China.
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200044, China.
authors.forename: Xianrong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Pathology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Institute of Pathology, Fudan University, Shanghai 200032, China.|Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Midie
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Pathology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Institute of Pathology, Fudan University, Shanghai 200032, China.|Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Weng
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Pathology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Institute of Pathology, Fudan University, Shanghai 200032, China.|Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Qiongyan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Pathology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Institute of Pathology, Fudan University, Shanghai 200032, China.|Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Yusi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Institute of Pathology, Fudan University, Shanghai 200032, China.|Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Pathology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Institute of Pathology, Fudan University, Shanghai 200032, China.|Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Du
mesh_terms: D000328:Adult; D055162:Biocatalysis; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D000072017:Deubiquitinating Enzymes; D018450:Disease Progression; D005260:Female; D000072278:Forkhead Box Protein M1 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011485:Protein Binding; D034622:RNA Interference; D054875:Ubiquitination
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D000072017:Deubiquitinating Enzymes; C538826:OTUB1 protein, human; D003546:Cysteine Endopeptidases
keywords: FOXM1; OTUB1; deubiquitination; ovarian carcinoma; ubiquitination