{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HSPA1A (commonly known as Hsp72) functions as a central cytoprotective molecular chaperone that safeguards cells from a wide range of proteotoxic stresses. It promotes refolding of misfolded proteins and facilitates the disaggregation and reactivation of stable protein aggregates through cooperation with other chaperones—for example, Hsp110 family members—in a process that restores native protein conformation (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " HSPA1A expression is rapidly induced in response to various stress stimuli—including oxidative stress, endoplasmic reticulum (ER) stress, and hyperthermia—which in turn improves cell survival by enhancing key signaling pathways such as IRE1α/XBP1 during ER stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In skeletal muscle, elevated HSPA1A levels correlate with increased mitochondrial biogenesis and improved oxidative metabolism, thereby contributing to enhanced insulin sensitivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the molecular level, HSPA1A modulates both protein synthesis and degradation: it interacts with nucleotide exchange factors and co‐chaperones such as members of the BAG family to orchestrate client protein handling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In doing so, HSPA1A not only impedes apoptotic signaling through direct binding and inhibition of kinases like ASK1—which attenuates downstream stress kinase cascades"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "—but also contributes to oncogenic cell survival. Indeed, in several cancers, heightened HSPA1A expression assists in sustaining the function of the Hsp90 chaperone machinery and can protect oncogenic regulators from proteasomal degradation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, scaffold functions of HSPA1A have been implicated in preventing the degradation of key transcription factors such as YBX1, thereby facilitating tumor-promoting signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Finally, regulation of HSPA1A expression and activity is integrated into the broader heat shock response, where factors such as eEF1A harmonize both transcriptional and post-transcriptional events to ensure an effective stress response"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", and its depletion sensitizes tumor cells to multiple apoptotic insults."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rayees U H Mattoo, Sandeep K Sharma, Smriti Priya, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hsp110 is a bona fide chaperone using ATP to unfold stable misfolded polypeptides and reciprocally collaborate with Hsp70 to solubilize protein aggregates."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.479253"}], "href": "https://doi.org/10.1074/jbc.M113.479253"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23737532"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23737532"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sanjeev Gupta, Ayswaria Deepti, Shane Deegan, et al. 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