Ubiquitin specific peptidase 28 (USP28)

Ubiquitin specific peptidase 28 (USP28) is a member of the ubiquitin-specific protease (USP) family of deubiquitinating enzymes. It functions as a cysteine protease that removes ubiquitin from target proteins, thus regulating their stability and activity. USP28 plays a key role in the regulation of oncogenic protein stability (notably c-Myc, CHK2, 53BP1, and LSD1), DNA damage response, cell cycle progression, and apoptosis. In cancer, USP28 is frequently overexpressed and has been shown to contribute to tumor cell proliferation, survival, DNA repair, and resistance to therapy. It interacts with the E3 ubiquitin ligase FBW7, antagonizing its degradation effects on oncogenic substrates, and may have context-dependent roles as both an oncogene and tumor suppressor. Due to its central role in pathways critical for cancer progression, USP28 is considered a promising yet complex therapeutic target, though no approved drugs currently target USP28 specifically[1][2][3].

Other names

Ubiquitin carboxyl-terminal hydrolase 28KIAA1515Deubiquitinating enzyme 28Ubiquitin thioesterase 28Ubiquitin-specific-processing protease 28

Deubiquitination and stabilization of key proteins involved in oncogenic pathways (e.g., c-Myc, CHK2, 53BP1, LSD1)\nModulation of DNA damage checkpoint signaling by controlling levels of repair and checkpoint proteins\nPromotion or suppression of tumor cell proliferation, depending on cellular context and FBW7 status