CUL3: A Promising Drug Target and Biomarker for the Treatment of Solid Tumors

Target Name: CUL3

NCBI ID: G8452

CUL3

CUL3: A Promising Drug Target and Biomarker for the Treatment of Solid Tumors

Abstract:

Cullin-3 (CUL3) is a protein that is expressed in various tissues, including the brain, pancreas, and gastrointestinal tract. Its unique structure and expression pattern have led to its potential as a drug target and biomarker for the treatment of solid tumors. This article discusses the biology of CUL3, its expression pattern in various tissues, and its potential as a drug target and biomarker.

Introduction:

Solid tumors are a leading cause of cancer-related mortality worldwide. Despite advances in cancer treatment, the survival rate for many types of solid tumors remains poor. Therefore, there is a need for new and effective drugs that can target these tumors and improve outcomes . One promising approach to cancer treatment is the use of drugs that target proteins that are over-expressed or mutated in tumors. One such protein is CUL3, which has been identified as a potential drug target and biomarker for the treatment of solid tumors.

Structure and Expression Pattern of CUL3:

Cullin-3 (CUL3) is a 21-kDa protein that is expressed in various tissues, including the brain, pancreas, and gastrointestinal tract. It is characterized by a unique structure that consists of a N-terminal alpha-helix, a middle alpha -helix, and a C-terminal alpha-helix. CUL3 is also characterized by the presence of a N-terminal signaling domain and a C-terminal carbohydrate-binding domain.

CUL3 is expressed in various tissues, including the brain, pancreas, and gastrointestinal tract, and has been shown to be involved in various physiological processes, including cell signaling, cell adhesion, and tissue homeostasis. It is also expressed in various types of cancer, including lung, breast, and colorectal cancer. Therefore, CUL3 may be a promising drug target for the treatment of solid tumors.

Potential as a Drug Target:

CUL3 has been shown to be involved in various signaling pathways that are involved in cancer progression. For example, studies have shown that CUL3 is involved in the PI3K/Akt signaling pathway, which is involved in cell signaling and proliferation. Additionally, CUL3 has been shown to be involved in the TGF-β signaling pathway, which is involved in cell proliferation, migration, and angiogenesis. Therefore, CUL3 may be a promising drug target for the treatment of solid tumors that are associated with these signaling pathways.

CUL3 has also been shown to interact with various drug targets, including inhibitors of the PI3K/Akt signaling pathway, such as perindopril and liraglutide. Additionally, CUL3 has also been shown to interact with anti-cancer drugs, such as taxanes and vinca alkaloids. Therefore , CUL3 may be an effective drug target for the treatment of solid tumors that are resistant to these drugs.

Potential as a Biomarker:

CUL3 has also been shown to be a potential biomarker for the treatment of solid tumors. Its unique expression pattern and structure have led to its potential as a diagnostic biomarker for cancer. For example, studies have shown that CUL3 is overexpressed in various types of cancer , including lung, breast, and colorectal cancer. Therefore, CUL3 may be a useful biomarker for the diagnosis and monitoring of these cancers.

In addition, CUL3 has also been shown to be involved in the development

Protein Name: Cullin 3

Functions: Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the BCR complex depends on the BTB domain-containing protein as the substrate recognition component. BCR(KLHL42) is involved in ubiquitination of KATNA1. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, BRMS1, MACROH2A1 and DAXX, GLI2 and GLI3. Can also form a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL; these complexes have lower ubiquitin ligase activity. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B) (PubMed:22358839, PubMed:27716508). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; by mediating ubiquitination of WNK4 (PubMed:23387299, PubMed:23453970, PubMed:23576762). The BCR(KLHL20) E3 ubiquitin ligase complex is involved in interferon response and anterograde Golgi to endosome transport: it mediates both ubiquitination leading to degradation and 'Lys-33'-linked ubiquitination (PubMed:20389280, PubMed:21840486, PubMed:21670212, PubMed:24768539). The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB (PubMed:19995937). The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation (PubMed:23455478). The BCR(KLHL22) ubiquitin ligase complex is also responsible for the amino acid-stimulated 'Lys-48' polyubiquitination and proteasomal degradation of DEPDC5. Through the degradation of DEPDC5, releases the GATOR1 complex-mediated inhibition of the TORC1 pathway (PubMed:29769719). The BCR(KLHL25) ubiquitin ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) (PubMed:22578813). The BCR(KLHL25) ubiquitin ligase complex is also involved in lipid synthesis by mediating ubiquitination and degradation of ACLY (PubMed:27664236). The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and TCOF1, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41 (PubMed:15983046). In concert with ATF2 and RBX1, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. The BCR(KCTD17) E3 ubiquitin ligase complex mediates ubiquitination and degradation of TCHP, a down-regulator of cilium assembly, thereby inducing ciliogenesis (PubMed:25270598). The BCR(KLHL24) E3 ubiquitin ligase complex mediates ubiquitination of KRT14, controls KRT14 levels during keratinocytes differentiation, and is essential for skin integrity (PubMed:27798626). The BCR(KLHL18) E3 ubiquitin ligase complex mediates the ubiquitination of AURKA leading to its activation at the centrosome which is required for initiating mitotic entry (PubMed:23213400). The BCR(KEAP1) E3 ubiquitin ligase complex acts as a key sensor of oxidative and electrophilic stress by mediating ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes (PubMed:15601839, PubMed:16006525). As part of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex functions mediates 'Lys-48' ubiquitination and proteasomal degradation of TIAM1 (PubMed:25684205). By controlling the ubiquitination of that RAC1 guanine exchange factors (GEF), regulates RAC1 signal transduction and downstream biological processes including the organization of the cytoskeleton, cell migration and cell proliferation (PubMed:25684205)

The "CUL3 Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about CUL3 comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

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