{"type": "root", "children": [{"type": "t", "text": "<head>\n <meta charset=\"UTF-8\">\n <title>DNAJB8 Function Summary</title>\n </head>\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n DNAJB8, a member of the Hsp40 (DNAJ) chaperone family, plays a multifaceted role in maintaining protein homeostasis and influencing cellular phenotypes involved in both neurodegenerative and oncogenic settings. In the context of protein misfolding disorders, DNAJB8 is a potent suppressor of aggregation of polyglutamine‐expanded proteins. Its anti‐aggregation function largely operates independently of the canonical N‐terminal J‐domain; instead, a unique C‐terminal serine‐rich region and acidic tail are critical for substrate binding, oligomer formation, and interactions with histone deacetylases, thereby forming a functional link between deacetylation pathways and chaperone activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer, DNAJB8 has emerged as an important molecule preferentially expressed in cancer stem‐like cells (CSCs). Its expression enhances the CSC phenotype by increasing tumor-initiating capacity and contributing to chemoresistance in renal and colon carcinomas. For instance, both overexpression and knockout studies in renal cancer models have demonstrated that DNAJB8 modulates the proportion of side-population cells and sphere formation, while being inducible by stress and regulated via heat shock factor 1 (HSF1)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " Moreover, its restricted expression pattern and immunogenicity—as a cancer/testis antigen—render DNAJB8 a promising target for CSC-directed immunotherapy, with preclinical evidence supporting both cytotoxic T cell and antibody-based approaches."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Structural studies further reveal that DNAJB8 exhibits intramolecular domain interactions—specifically between its J-domain and C-terminal region—that may function as a reversible switch to modulate its ability to recruit Hsp70, thereby fine-tuning its chaperone activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In colon cancer, additional findings indicate that DNAJB8 can interact with key regulators such as TP53 to prevent their degradation, contributing to chemoresistance to agents like oxaliplatin."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings position DNAJB8 as a versatile chaperone that not only prevents pathogenic protein aggregation in neurological disorders but also supports malignant phenotypes in cancer by promoting CSC maintenance and therapy resistance. This dual functionality makes DNAJB8 an attractive candidate for therapeutic targeting in both neurodegenerative and oncologic conditions.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jurre Hageman, Maria A Rujano, Maria A W H van Waarde, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A DNAJB chaperone subfamily with HDAC-dependent activities suppresses toxic protein aggregation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2010.01.001"}], "href": "https://doi.org/10.1016/j.molcel.2010.01.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20159555"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20159555"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Judith Gillis, Sabine Schipper-Krom, Katrin Juenemann, et al. 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