{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CCT2, also known as CCTβ, is a critical subunit of the multi‐protein chaperonin complex TRiC/CCT that plays multifaceted roles in cellular proteostasis. Its function spans from facilitating the folding of key client proteins involved in cell cycle progression and telomere maintenance to regulating autophagic clearance of aggregation‐prone proteins. For example, in estrogen‐responsive breast cancer cells, upregulated CCT2 appears to contribute to cell cycle regulation and tumor cell growth, making it a potential biomarker and therapeutic target in this context."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Moreover, as a key component of TRiC, CCT2 is essential for the proper folding of the telomerase cofactor TCAB1, which is necessary for telomere elongation and thus impacts cellular immortality."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Recent findings also reveal that CCT2 functions as an autophagy receptor that specifically promotes the degradation of solid protein aggregates via aggrephagy, highlighting its role in maintaining protein quality control in neuronal and brain tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, genetic studies have identified that mutations in CCT2 can lead to protein instability and impaired interactions with adjacent chaperonin subunits, contributing to pathological conditions such as Leber congenital amaurosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Disruption of CCT2’s interactions—for instance, its binding with β‐tubulin—has been shown to trigger apoptotic signaling in cancer cells, especially in scenarios involving chemoresistance, thereby underscoring its importance in cell survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " The role of CCT2 is evolutionarily conserved, as studies in Caenorhabditis elegans reveal that the orthologous cct genes exhibit similar structures and functions in maintaining proper protein folding."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, under hypoxic conditions in colorectal cancer, CCT2 has been implicated in the folding and stabilization of oncogenic factors such as Gli-1, thereby contributing to tumor progression and suggesting its viability as a novel therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Collectively, these studies highlight that CCT2 is indispensable not only for the efficient folding of a wide array of essential proteins but also for regulating autophagy and modulating tumorigenesis, with its dysregulation contributing to diverse human diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "A H Charpentier, A K Bednarek, R L Daniel, et al. 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