Drug Target and Biomarker: CXCR4 (G7852)

NCBI ID: G7852

CXCR4

Drug Target and Biomarker: CXCR4

WHIM mutations in CXCR4 result in a gain of G protein-dependent functions and stabilize the mutant receptor on the cell surface, leading to a gain-of-function.

CXCR4 has been targeted in the development of nanomedicines for cancer treatment.

The localization of CXCR4 on the plasma membrane affects its function, and cells with low plasma membrane CXCR4 expression show increased agonist-induced transcript levels of EGR1. This indicates that intracellular pools of CXCR4 are physiologically relevant and dependent on beta-arrestin-1.

A soluble presentation of SDF-1alpha molecules leads to transient signaling through CXCR4, while matrix-bound presentation of SDF-1alpha results in sustained and intensified signaling through CXCR4 and hyaluronan receptors, activating Rac1 and pERK.

Chemokine signals involving Sdf1 and Cxcr4 play a role in tissue regeneration, where Sdf1 recruits Cxcr4+ leukocytes to promote fibrosis and scar formation. Disruption of Sdf1-Cxcr4 signaling can enhance tissue repair.

CXCR4 is recruited and accumulates at the immunological synapse (IS) during antigen recognition by CD4+ T cells.

During IS formation, CXCR4 redistributes to specific areas known as the pSMAC and dSMAC.

Drebrin, a protein associated with F-actin, is involved in the accumulation of CXCR4 at the IS.

Drebrin is also specifically enriched at the virological synapse (VS) formed during HIV-1 binding to CD4+ T cells, and it partially co-localizes with the internalized virus.

In the absence of CXCL12, a signaling molecule, LASP1 is phosphorylated and remains bound to CXCR4, while Ago2, another protein, uses Let-7a to repress motility-related targets.

When CXCR4 is stimulated with CXCL12, LASP1 undergoes dephosphorylation and phosphorylation at different sites, which alters the interaction between LASP1 and Ago2 and affects Let-7a driven RNA interference (RNAi).

LASP1 can interfere with Let-7a driven RNAi by either binding to Let-7a-bound Ago2 and interfering with target binding or by binding to Ago2 and preventing Ago2 from binding to Let-7a.

Expression of Let-7a target genes, such as eIF4G2, vinculin, CCR7, and cyclin D1, can be altered in a LASP1-Ago2 interaction-dependent manner.

The profile of the endogenous targets Let-7a differed from the results of a luciferase reporter assay.

Protein Name: C-X-C Motif Chemokine Receptor 4

Functions: Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:28978524, PubMed:18799424, PubMed:24912431). Involved in the AKT signaling cascade (PubMed:24912431). Plays a role in regulation of cell migration, e.g. during wound healing (PubMed:28978524). Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels (PubMed:20228059). Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Involved in hematopoiesis and in cardiac ventricular septum formation. Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in cerebellar development. In the CNS, could mediate hippocampal-neuron survival (By similarity)

The "CXCR4 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 CXCR4 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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