Journal
MOLECULAR CELL
Volume 29, Issue 1, Pages 102-111Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2007.12.015
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Funding
- NCI NIH HHS [R01 CA098172-06, CA090465, R01 CA098172-05, R01 CA090465-06, R01 CA098172-04, R01 CA098172, R01 CA090465-06S1, R01 CA078831, R01 CA090465-05, CA098172, R01 CA090465] Funding Source: Medline
- NIGMS NIH HHS [R01 GM055360, T32 GM008216, GM55360] Funding Source: Medline
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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.
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