Emerging Roles of Calreticulin in Cancer: Implications for Therapy
| Autor: | Bilikere S. Dwarakanath, Amit Verma, Kailash Manda, Kavya Venkateswaran, Anju Shrivastava, Ashok K. Prasad, Anant Narayan Bhatt, Virinder S. Parmar, Christophe Len, Hanumantharao G. Raj |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell Survival medicine.medical_treatment Antineoplastic Agents Biology Endoplasmic Reticulum medicine.disease_cause Biochemistry Epigenesis Genetic 03 medical and health sciences Acetyltransferases Neoplasms medicine Animals Humans Cell adhesion Molecular Biology Cell Proliferation Cell Death Endoplasmic reticulum Cell Membrane Cell Biology General Medicine Immunotherapy Cell biology 030104 developmental biology biology.protein Immunogenic cell death Histone deacetylase Signal transduction Calreticulin Carcinogenesis Signal Transduction |
| Zdroj: | Current Protein & Peptide Science. 19:344-357 |
| ISSN: | 1389-2037 |
| Popis: | Calreticulin (CRT), initially identified as a ubiquitous calcium-binding protein in the endoplasmic reticulum, has emerged as a multifunctional protein with roles in calcium homeostasis, molecular chaperoning and cell adhesion. Emerging evidence suggests its involvement in tumorigenesis facilitating proliferation, migration, and adhesion. CRT translocated to the cell surface (ecto-CRT) serves as a phagocytic signal for immunogenic cell death (ICD) mediated through dendritic cells (DCs) and cytotoxic T-cell activation thereby making tumors susceptible to immunotherapy-based anti-cancer strategies. CRT is now regarded as one of the most potent danger-associated molecular patterns (DAMPs) with the ecto-CRT triggering restoration of homeostasis by immune stimulation. A recently identified novel transacetylase activity of CRT adds a new dimension to its multi-faceted involvement in cancer by virtue of polyphenolic acetates (PA): CRT transacetylase (CRTase) system which results in hyperacetylation of target proteins, thereby mimicking the effects of Histone deacetylase inhibitors (HDACi). Since protein acetylation is one of the crucial post-translational modifications (PTMs) influencing the epigenetic regulation and signal transduction, CRT can be a potential target for developing anticancer therapeutics and preventive strategies by employing pharmacologically compatible semi-synthetic acetyl donors like polyphenolic acetates and other agents. |
| Databáze: | OpenAIRE |
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