Disabled-2 (Dab2/DOC-2) is a mitogen-responsive adaptor protein required for multiple cellular functions. It is involved in many signaling pathways and plays an integral role in vesicular uptake and trafficking, modulating immune function, protein-protein interactions, cellular homeostasis and differentiation, oncogenesis, and inflammatory processes in organ systems. It contains domains for binding to NPXY motif-containing and SH3 domain-containing adapter proteins, phosphoinositides, glycoprotein 100 (gp100, or megalin), integrins, clathrin, and myosin VI. However, the molecular mechanism(s) of Dab2's biological function still remain to be elucidated. In this review, we provide an extensive up-to-date understanding of the function of Dab2 and its regulation in cardiovascular diseases, immune disorders, tumorigenesis, and central nervous system disorders.
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dab2 is required for the scavenging function of lymphatic endothelial cells in the zebrafish meninges.
Sci Rep
November 2024
Institute for Cardiovascular Organogenesis and Regeneration, Faculty of Medicine, University of Münster, Röntgenstraße 16, 48149, Münster, Germany.
To date it is only partially understood how the brain is cleared of waste products resulting from its high metabolic activity, although this process has important implications for the development and progression of neurodegenerative diseases. Lymphatic vessels play a central role in maintaining fluid and tissue homeostasis, and the recent description of meningeal lymphatic vessels within the dura mater of mice, human and zebrafish has raised considerable interest in unraveling the function of these vessels. In zebrafish, brain lymphatic endothelial cells (BLECs) constitute an additional meningeal lymphatic endothelial cell population.
View Article and Find Full Text PDFDisabled 2 (Dab2) Regulates Tumour Progression in Skin Squamous Cell Carcinoma.
Exp Dermatol
November 2024
Stem Cell Biology Group, Waghmare Lab, Cancer Research Institute, Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, India.
Dab2 is an endocytic adaptor protein involved in various physiological processes and signaling pathways. Dab2 is deregulated in various cancers; however, its role in skin squamous cell carcinoma ( SCC) has not been elucidated yet. In the present study, we used the DMBA/TPA induced murine skin carcinogenesis model to examine the role of Dab2 in skin tumour progression.
View Article and Find Full Text PDFThe scaffold protein disabled 2 (DAB2) and its role in tumor development and progression.
Mol Biol Rep
June 2024
Department of Pharmacology and Pharmacy Practice, K. B. Institute of Pharmaceutical Education and Research, Gandhinagar, Gujarat, 382023, India.
Background: Disabled 2 (DAB2) is a multifunctional protein that has emerged as a critical component in the regulation of tumor growth. Its dysregulation is implicated in various types of cancer, underscoring its importance in understanding the molecular mechanisms underlying tumor development and progression. This review aims to unravel the intricate molecular mechanisms by which DAB2 exerts its tumor-suppressive functions within cancer signaling pathways.
View Article and Find Full Text PDFDab2 (Disabled-2), an adaptor protein, regulates self-renewal of hair follicle stem cells.
Commun Biol
May 2024
Stem Cell Biology Group, Waghmare Lab, Cancer Research Institute, Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, Maharashtra, India.
Disabled 2 (Dab2), an adaptor protein, is up regulated in the hair follicle stem cells (HFSCs); however, its role in any tissue stem cells has not been studied. In the present study, we have reported that Dab2 conditional knockout (Dab2-cKO) mice exhibited a delay in the HF cycle due to perturbed activation of HFSCs. Further, Dab2-cKO mice showed a reduction in the number of HFSCs and reduced colony forming ability of HFSCs.
View Article and Find Full Text PDFDisable 2, A Versatile Tissue Matrix Multifunctional Scaffold Protein with Multifaceted Signaling: Unveiling Role in Breast Cancer for Therapeutic Revolution.
Cell Biochem Biophys
June 2024
Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Navrangpura, Ahmedabad, 380009, Gujarat, India.
The Disabled-2 (DAB2) protein, found in 80-90% of various tumors, including breast cancer, has been identified as a potential tumor suppressor protein. On the contrary, some hypothesis suggests that DAB2 is associated with the modulation of the Ras/MAPK pathway by endocytosing the Grb/Sos1 signaling complex, which produces oncogenes and chemoresistance to anticancer drugs, leading to increased tumor growth and metastasis. DAB2 has multiple functions in several disorders and is typically under-regulated in several cancers, making it a potential target for treatment of cancer therapy.
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