{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CHERP is a multifunctional protein that plays a critical role in both intracellular Ca²⁺ signaling and RNA processing. Initially characterized as an endoplasmic reticulum‐resident protein, CHERP was shown to modulate Ca²⁺ release by interacting with key channels such as the inositol 1,4,5‐trisphosphate and ryanodine receptors, thereby influencing calcium‐dependent pathways including NFAT activation and cell cycle progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " More recent studies have revealed that CHERP also localizes to the nucleus, where it associates with components of the spliceosome—interacting with factors such as U2 snRNA spliceosomal proteins, ALG‑2, RBM17, and SR140—to regulate alternative splicing of critical transcripts (including those for the inositol 1,4,5‑trisphosphate receptor and RNA surveillance factors) that impact cell proliferation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": " In oncogenic settings, elevated CHERP expression has been associated with enhanced tumor cell proliferation and poor clinical outcomes in cancers such as colorectal cancer and neuroblastoma, while its depletion triggers DNA damage responses, cell cycle arrest, and apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, interactions between CHERP and extracellular matrix components—demonstrated by its binding to specific motifs within the G1 tandem repeats of aggrecan—further underscore its versatile role in cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Collectively, these findings establish CHERP as a pivotal mediator linking Ca²⁺ homeostasis with post‐transcriptional splicing regulation, thereby influencing both normal cellular function and oncogenic processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Flavia A O'Rourke, Janice M LaPlante, Maurice B Feinstein "}, {"type": "b", "children": [{"type": "t", "text": "Antisense-mediated loss of calcium homoeostasis endoplasmic reticulum protein (CHERP; ERPROT213-21) impairs Ca2+ mobilization, nuclear factor of activated T-cells (NFAT) activation and cell proliferation in Jurkat T-lymphocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20030013"}], "href": "https://doi.org/10.1042/BJ20030013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12656674"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12656674"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Timothy Ryan, Parveen Sharma, Alex Ignatchenko, et al. 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