Ubiquitin carboxyl-terminal hydrolase MINDY-1 (MINDY1)

Ubiquitin carboxyl-terminal hydrolase MINDY-1 (MINDY1) is a highly selective deubiquitinating enzyme (DUB) of the cysteine protease type that specifically cleaves K48-linked polyubiquitin chains from substrate proteins, which commonly tags those proteins for degradation by the proteasome. MINDY1 acts by trimming ubiquitin chains from the distal end, showing substrate and chain length specificity via multiple ubiquitin-binding domains within its catalytic core. It is structurally distinct from other DUBs, utilizing a non-canonical catalytic triad (Cys-His-Thr) and being regulated by autoinhibition relieved upon substrate engagement[1][2][4]. Functionally, MINDY1 participates in the regulation of protein degradation, cell cycle, signal transduction, and proteostasis. Disease associations include breast cancer, where MINDY1 stabilizes estrogen receptor α, promoting tumor cell proliferation and potentially influencing tamoxifen response[5]. While no direct drugs targeting MINDY1 are yet in clinical use, its selectivity and disease relevance make it a potential therapeutic target in cancer and disorders of protein homeostasis.

Other names

FAM63AKIAA1390MINDY-1MIU-containing novel DUB family member 1Deubiquitinating enzyme MINDY-1Protein FAM63AMotif interacting with Ub-containing novel DUBFamily with sequence similarity 63 member A

Cleavage/removal of K48-linked polyubiquitin chains from substrates, regulating their proteasomal degradation Stabilization of specific protein targets, such as estrogen receptor α, via deubiquitination[5]