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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing / analysis
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Adaptor Proteins, Signal Transducing / physiology
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Biomarkers
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Carcinoma, Non-Small-Cell Lung / pathology
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Cell Cycle / physiology*
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Cell Line, Transformed / cytology
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Cell Line, Transformed / metabolism
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Cell Line, Tumor / cytology
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Cell Line, Tumor / metabolism
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Gene Expression Profiling*
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Histone Acetyltransferases / analysis
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Histone Acetyltransferases / physiology
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Humans
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Lung Neoplasms / pathology
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Neoplastic Stem Cells / cytology
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Neoplastic Stem Cells / metabolism*
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Nuclear Proteins / analysis
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Nuclear Proteins / physiology
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Promoter Regions, Genetic / genetics
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Protein Processing, Post-Translational / physiology*
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Protein Subunits
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Proto-Oncogene Proteins c-myc / physiology
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Recombinant Fusion Proteins / physiology
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Thiolester Hydrolases / physiology*
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Trans-Activators / physiology*
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Transcription Factors / chemistry*
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Transcription Factors / physiology
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Transcription, Genetic / physiology*
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Ubiquitin Thiolesterase
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Ubiquitination / physiology*
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p300-CBP Transcription Factors / analysis
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p300-CBP Transcription Factors / physiology
Substances
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Adaptor Proteins, Signal Transducing
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Biomarkers
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MYC protein, human
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Nuclear Proteins
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Protein Subunits
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Proto-Oncogene Proteins c-myc
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Recombinant Fusion Proteins
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Trans-Activators
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Transcription Factors
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transformation-transcription domain-associated protein
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Histone Acetyltransferases
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p300-CBP Transcription Factors
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p300-CBP-associated factor
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Thiolester Hydrolases
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Ubiquitin Thiolesterase
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Usp22 protein, human