title: The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression.
abstract: Polycomb genes encode critical regulators of both normal stem cells and cancer stem cells. A gene signature that includes Polycomb genes and additional genes coregulated with Polycomb genes was recently identified. The expression of this signature has been reported to identify tumors with the cancer stem cell phenotypes of aggressive growth, metastasis, and therapy resistance. Most members of this 11 gene signature encode proteins with well-defined roles in human cancer. However, the function of the signature member USP22 remains unknown. We report that USP22 is a previously uncharacterized subunit of the human SAGA transcriptional cofactor complex. Within SAGA, USP22 deubiquitylates histone H2B. Furthermore, USP22 is recruited to specific genes by activators such as the Myc oncoprotein, where it is required for transcription. In support of a functional role within the Polycomb/cancer stem cell signature, USP22 is required for appropriate progression through the cell cycle.
authors.affiliation: The Department of Cancer Biology, The Kimmel Cancer Center, Thomas Jefferson Medical College, Philadelphia, PA 19107, USA.
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Zhang
authors.forename: Maya
authors.initials: M
authors.lastname: Varthi
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Sykes
authors.forename: Charles
authors.initials: C
authors.lastname: Phillips
authors.forename: Claude
authors.initials: C
authors.lastname: Warzecha
authors.forename: Wenting
authors.initials: W
authors.lastname: Zhu
authors.forename: Anastasia
authors.initials: A
authors.lastname: Wyce
authors.forename: Alan W
authors.initials: AW
authors.lastname: Thorne
authors.forename: Shelley L
authors.initials: SL
authors.lastname: Berger
authors.forename: Steven B
authors.initials: SB
authors.lastname: McMahon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000502:physiology; D015415:Biomarkers; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology*; D002461:Cell Line, Transformed / Q000166:cytology / Q000378:metabolism; D045744:Cell Line, Tumor / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D051548:Histone Acetyltransferases / Q000032:analysis / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000032:analysis / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D021122:Protein Subunits; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013869:Thiolester Hydrolases / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry* / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*; D043222:Ubiquitin Thiolesterase; D054875:Ubiquitination / Q000502:physiology*; D050880:p300-CBP Transcription Factors / Q000032:analysis / Q000502:physiology; D000099224:p300-CBP-Associated Factor
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D051548:Histone Acetyltransferases; D009687:Nuclear Proteins; D021122:Protein Subunits; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D013869:Thiolester Hydrolases; D015534:Trans-Activators; D014157:Transcription Factors; D043222:Ubiquitin Thiolesterase; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C489427:MYC protein, human; C113829:transformation-transcription domain-associated protein; C527170:Usp22 protein, human