title: USP10 antagonizes c-Myc transcriptional activation through SIRT6 stabilization to suppress tumor formation.
abstract: The reduced protein expression of SIRT6 tumor suppressor is involved in tumorigenesis. The molecular mechanisms underlying SIRT6 protein downregulation in human cancers remain unknown. Using a proteomic approach, we have identified the ubiquitin-specific peptidase USP10, another tumor suppressor, as one of the SIRT6-interacting proteins. USP10 suppresses SIRT6 ubiquitination to protect SIRT6 from proteasomal degradation. USP10 antagonizes the transcriptional activity of the c-Myc oncogene through SIRT6, as well as p53, to inhibit cell-cycle progression, cancer cell growth, and tumor formation. To support this conclusion, we detected significant reductions in both USP10 and SIRT6 protein expression in human colon cancers. Our study discovered crosstalk between two tumor-suppressive genes in regulating cell-cycle progression and proliferation and showed that dysregulated USP10 function promotes tumorigenesis through SIRT6 degradation.
authors: Department of Pathology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.
authors: Zhenghong
authors: Z
authors: Lin
authors: Department of Pathology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.
authors: Heeyoung
authors: H
authors: Yang
authors: Department of Pathology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.
authors: Can
authors: C
authors: Tan
authors: Department of Pathology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.
authors: Jinping
authors: J
authors: Li
authors: Department of Pathology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.
authors: Zhaojian
authors: Z
authors: Liu
authors: Department of Pathology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.
authors: Qiu
authors: Q
authors: Quan
authors: Department of Pathology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.
authors: Sinyi
authors: S
authors: Kong
authors: Department of Pathology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.
authors: Junsheng
authors: J
authors: Ye
authors: Department of Pathology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.
authors: Beixue
authors: B
authors: Gao
authors: Department of Pathology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA. Electronic address: fangd@northwestern.edu.
authors: Deyu
authors: D
authors: Fang
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000378:metabolism; D055550:Protein Stability; D059748:Proteolysis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; C431363:USP10 protein, human; D043222:Ubiquitin Thiolesterase; C516592:SIRT6 protein, human; D037761:Sirtuins