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.
Keywords: Calreticulin, immunogenic cell death, danger-associated molecular patterns, protein acetylation, polyphenolic acetates,
calreticulin transacetylase, cancer therapy.
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