Zhen Y, Knobel PA, Stracker TH, Reverter D

Ubiquitin-Specific Protease 28 (USP28) is a deubiquitinating enzyme that has been implicated in the DNA damage response (DDR), the regulation of Myc signaling and cancer progression. The half-life stability of major regulators of critical cellular pathways depends on the activities of specific ubiquitin E3 ligases that target them for proteosomal ...

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degradation and deubiquitinating enzymes that promote their stabilization. One function of the post-translational Small Ubiquitin Modifier (SUMO) is the regulation of enzymatic activity of protein targets. In this work we demonstrate that the SUMO modification of the N-terminal domain of USP28 negatively regulates its deubiquitinating activity, revealing a role for the N-terminal region as a regulatory module in the control of USP28 activity. Despite the presence of ubiquitin-binding domains in the N-terminal domain, its truncation does not impair de-ubiquitinating activity on di-ubiquitin or poly-ubiquitin chain substrates. In contrast to other characterized USP de-ubiquitinases, our results indicate that USP28 has a chain preference activity for K11, K48 and K63 di-ubiquitin linkages.

Date: Oct. 30, 2014

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