USP32 deubiquitinase: cellular functions, regulatory mechanisms, and potential as a cancer therapy target

Abstract

An essential protein regulatory system in cells is the ubiquitin-proteasome pathway. The substrate is modified by the ubiquitin ligase system (E1-E2-E3) in this pathway, which is a dynamic protein bidirectional modification regulation system. Deubiquitinating enzymes (DUBs) are tasked with specifically hydrolyzing ubiquitin molecules from ubiquitin-linked proteins or precursor proteins and inversely regulating protein degradation, which in turn affects protein function. The ubiquitin-specific peptidase 32 (USP32) protein level is associated with cell cycle progression, proliferation, migration, invasion, and other cellular biological processes. It is an important member of the ubiquitin-specific protease family. It is thought that USP32, a unique enzyme that controls the ubiquitin process, is closely linked to the onset and progression of many cancers, including small cell lung cancer, gastric cancer, breast cancer, epithelial ovarian cancer, glioblastoma, gastrointestinal stromal tumor, acute myeloid leukemia, and pancreatic adenocarcinoma. In this review, we focus on the multiple mechanisms of USP32 in various tumor types and show that USP32 controls the stability of many distinct proteins. Therefore, USP32 is a key and promising therapeutic target for tumor therapy, which could provide important new insights and avenues for antitumor drug development. The therapeutic importance of USP32 in cancer treatment remains to be further proven. In conclusion, there are many options for the future direction of USP32 research.

USP32 facilitates non-small cell lung cancer progression via deubiquitinating BAG3 and activating RAF-MEK-ERK signaling pathway

“…The drug bortezomib has been used in multiple myeloma as a proteasome inhibitor to interfere with the UPS pathway [45]. As a member of the class of deubiquitinating enzymes, USP32 has been linked to the beginnings and progression of several malignancies and has been recognized as an oncogene [11]. It has been found that USP32 is abundantly expressed in gastric cancer and that it regulates chemoresistance in GC and SMAD2 cells [46].…”

“…The DUB family member ubiquitin-speci c peptidase 32 (USP32) has several structural domains that are involved in its function. It also has the most signi cant structural domain among USP members, the USP catalytic domain [11,12]. USP6 and PoUSP32, as two homologs of USP32, share functional enzymatic structural domains and perform similar physiological functions as USP32 [13,14].…”

“…USP6 and PoUSP32, as two homologs of USP32, share functional enzymatic structural domains and perform similar physiological functions as USP32 [13,14]. USP32 is broadly distributed in human tissues, with the testis being the most highly expressed organ [11]. Research has demonstrated that USP32 is expressed in the cytoplasm as well as the cell membrane.…”

“…It is also one of the few DUBs connected to the endocytosis pathway that can regulate the function of a number of factors [15,16]. In the meantime, USP32 participates in physiological processes like cell cycle, invasion, migration, multiplication of cells, and repair of DNA damage [11]. Aberrant expression of USP32 triggers certain diseases such as Parkinson's, Fragile X Syndrome, Chronic Kidney Disease and Cancer [11,[17][18][19].…”

“…In the meantime, USP32 participates in physiological processes like cell cycle, invasion, migration, multiplication of cells, and repair of DNA damage [11]. Aberrant expression of USP32 triggers certain diseases such as Parkinson's, Fragile X Syndrome, Chronic Kidney Disease and Cancer [11,[17][18][19]. Recent research has demonstrated the high expression of USP32 in a range of cancers [20][21][22][23][24][25][26] and its role in the initiation and progression of cancer.…”