Inhibitor of DNA-binding (ID) proteins are key developmental regulators that block cellular differentiation in multiple tissues. Because the members of the ID family (ID1–4) are highly expressed in pluripotent cells and aberrantly stabilized in tumors, they are believed to play critical roles in cancer stem cell biology. Williams and colleagues performed a screen of human deubiquitinases (DUB) to identify candidates whose overexpression could increase ID2 levels, and found that ubiquitin-specific peptidase 1 (USP1) specifically stabilized, bound, and deubiquitinated ID2 in vitro. Analysis of USP1 gene expression patterns revealed that this DUB is more highly expressed in osteosarcoma samples compared to normal bone and correlates with high ID2 protein levels. It remains unclear how USP1 is upregulated, but amplification of the USP1 locus has been identified in a subset of osteosarcomas. In osteosarcoma cell lines, USP1 knockdown led to decreased levels of ID1, ID2, and ID3 (ID4 is not proteasomally...

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