Target Name: USP36
NCBI ID: G57602
Other Name(s): ubiquitin thioesterase 36 | ubiquitin-specific-processing protease 36 | Ubiquitin-specific-processing protease 36 | deubiquitinating enzyme 36 | DUB1 | ubiquitin specific peptidase 36 | Deubiquitinating enzyme 1 | Ubiquitin thioesterase 36 | Ubiquitin thiolesterase 36 | UBP36_HUMAN | ubiquitin specific protease 36 | Deubiquitinating enzyme 36 | Ubiquitin carboxyl-terminal hydrolase 36 | Ubiquitin specific peptidase 36 | Ubiquitin specific protease 36 | KIAA1453

USP36: A Potential Drug Target and Biomarker for Ubiquitin-Proteasome Complex

The ubiquitin-proteasome complex (UPC) is a highly conserved protein complex that plays a crucial role in regulating protein degradation in the cell. It is a complex of various proteins that work together to identify and remove damaged or unnecessary proteins from the cell, thereby maintaining cellular homeostasis. One of the key proteins in this complex is USP36, which is a member of theBec family of ubiquitin enzymes.

USP36 is a 21-kDa protein that contains a catalytic active site, a regulatory interface, and a C-terminal ubiquitin-like domain (ULD). It is widely expressed in various tissues and cells and is involved in the regulation of protein degradation, cell signaling, and DNA replication. USP36 has been implicated in various cellular processes, including cell growth, apoptosis, and neurodegeneration.

Given its involvement in numerous cellular processes, USP36 has naturally emerged as a potential drug target. Recent studies have suggested that inhibiting USP36 activity may be a promising approach for treating various diseases, including neurodegenerative disorders, cancer, and autoimmune diseases.

One of the key challenges in targeting USP36 is its high structural complexity, as it contains multiple domains with diverse functions. Therefore, there is a need for new inhibitors that can specifically target the USP36 active site. Several studies have reported the synthesis of various inhibitors that target the USP36 active site, including serine protease (SPE) inhibitors, Beclin-1 inhibitors, and UPD inhibitors (5,6).

In addition to its potential as a drug target, USP36 has also been identified as a potential biomarker for various diseases. The Ubiquitin-Proteasome Complex has been implicated in the development and progression of various diseases, including neurodegenerative disorders, cancer, and neuroinflammation (7 ). Therefore, measuring the levels of USP36 in various biological samples, such as brain tissue, may provide valuable information for the diagnosis and prognosis of these diseases.

To further explore the potential of USP36 as a biomarker, several studies have investigated the expression and distribution of USP36 in various biological samples, including brain tissue (8,9). These studies have shown that USP36 is highly expressed in the brain and that its levels are decreased in various neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease.

Furthermore, some studies have suggested that USP36 may be involved in the pathogenesis of cancer. Several studies have reported that USP36 is overexpressed in various cancer tissues and that its levels are associated with cancer progression and poor prognosis (10,11). Therefore, targeting USP36 may be a promising approach for the development of new cancer therapies.

In conclusion, USP36 is a protein that plays a crucial role in the ubiquitin-proteasome complex and has been implicated in various cellular processes, including cell growth, apoptosis, and neurodegeneration. Its high structural complexity and multiple domains make it a challenging target for new inhibitors. However, recent studies have reported the synthesis of several inhibitors that target the USP36 active site, and its potential as a biomarker for various diseases, including neurodegenerative disorders, cancer, and neuroinflammation. Further research is needed to fully explore the potential of USP36 as a drug target and biomarker.

Protein Name: Ubiquitin Specific Peptidase 36

Functions: Deubiquitinase essential for the regulation of nucleolar structure and function (PubMed:29273634, PubMed:19208757, PubMed:22902402). Required for cell and organism viability (PubMed:29273634, PubMed:19208757, PubMed:22902402). Plays an important role in ribosomal RNA processing and protein synthesis, which is mediated, at least in part, through deubiquitination of DHX33, NPM1 and FBL, regulating their protein stability (PubMed:29273634, PubMed:19208757, PubMed:22902402). Functions as a transcriptional repressor by deubiquiting histone H2B at the promoters of genes critical for cellular differentiation, such as CDKN1A, thereby preventing histone H3 'Lys-4' trimethylation (H3K4) (PubMed:29274341). Specifically deubiquitinates MYC in the nucleolus, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 3 of FBXW7 (FBW7gamma) in the nucleolus and counteracting ubiquitination of MYC by the SCF(FBW7) complex (PubMed:25775507). In contrast, it does not interact with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm (PubMed:25775507). Interacts to and regulates the actions of E3 ubiquitin-protein ligase NEDD4L over substrates such as NTRK1, KCNQ2 and KCNQ3, affecting their expression an functions (PubMed:27445338). Deubiquitinates SOD2, regulates SOD2 protein stability (PubMed:21268071). Deubiquitinase activity is required to control selective autophagy activation by ubiquitinated proteins (PubMed:22622177). Promotes CEP63 stabilization through 'Lys-48'-linked deubiquitination leading to increased stability (PubMed:35989368)

More Common Targets

USP37 | USP38 | USP39 | USP4 | USP40 | USP41 | USP42 | USP43 | USP44 | USP45 | USP46 | USP46-DT | USP47 | USP48 | USP49 | USP5 | USP50 | USP51 | USP53 | USP54 | USP6 | USP6NL | USP6NL intronic transcript 1 (non-protein coding), transcript variant 1 | USP7 | USP8 | USP8P1 | USP9X | USP9Y | USPL1 | UST | UTF1 | UTP11 | UTP14A | UTP14C | UTP15 | UTP18 | UTP20 | UTP23 | UTP25 | UTP3 | UTP4 | UTP6 | UTRN | UTS2 | UTS2B | UTS2R | UTY | UVRAG | UVSSA | UXS1 | UXT | UXT-AS1 | VAC14 | Vacuolar H+ ATPase | VAMP1 | VAMP2 | VAMP3 | VAMP4 | VAMP5 | VAMP7 | VAMP8 | VANGL1 | VANGL2 | VAPA | VAPB | VARS1 | VARS2 | Vascular endothelial growth factor receptor (VEGFR) | Vascular endothelial growth factors (VEGF) | VASH1 | VASH1-AS1 | VASH2 | VASN | Vasoactive intestinal polypeptide receptor (VIP-R) | Vasohibin | Vasopressin Receptor | Vasopressin V1 Receptor | VASP | VAT1 | VAT1L | VAV1 | VAV2 | VAV3 | VAV3-AS1 | VAX1 | VAX2 | VBP1 | VCAM1 | VCAN | VCL | VCP | VCPIP1 | VCPKMT | VCX | VCX2 | VCX3A | VCX3B | VCY | VCY1B | VDAC1