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POH1/Rpn11/PSMD14: a journey from basic research in fission yeast to a prognostic marker and a druggable target in cancer cells by Vito Spataro; Antoine Buetti-Dinh is a Medicine article available to read on EtoBox.

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## Abstract POH1/Rpn11/PSMD14 is a highly conserved protein in eukaryotes from unicellular organisms to human and has a crucial role in cellular homoeostasis. It is a subunit of the regulatory particle of the proteasome, where it acts as an intrinsic deubiquitinase removing polyubiquitin chains from substrate proteins. This function is not only coupled to the translocation of substrates into the core of the proteasome and their subsequent degradation but also, in some instances, to the stabilisation of ubiquitinated proteins through their deubiquitination. POH1 was initially discovered as a functional homologue of the fission yeast gene pad1^+^, which confers drug resistance when overexpressed. In translational studies, expression of POH1 has been found to be increased in several tumour types relative to normal adjacent tissue and to correlate with tumour progression, higher tumour grade, decreased sensitivity to cytotoxic drugs and poor prognosis. Proteasome inhibitors targeting the core particle of the proteasome are highly active in the treatment of myeloma, and recently developed POH1 inhibitors, such as capzimin and thiolutin, have shown promising anticancer activity in cell l

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Author

Vito Spataro; Antoine Buetti-Dinh

Publisher

Springer Science and Business Media LLC

Published

2022

Language

EN

Field

Medicine (Health Sciences)