{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ICE1 is a multifunctional protein with context‐dependent roles in metazoans and plants. In mammalian cells, ICE1 (also known as KIAA0947) contributes to RNA quality control by promoting nonsense‐mediated mRNA decay through its putative MIF4G domain, which facilitates the association of the NMD protein UPF3B with the exon junction complex."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Additionally, ICE1 functions as a component of the little elongation complex that regulates RNA polymerase II–dependent transcription; here, its interaction with ELL/EAF is modulated by p53, thereby influencing the assembly of snRNP complexes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " ICE1 has also emerged as a candidate gene within a critical region of terminal 5p deletions associated with Cri‐du‐Chat syndrome, implying a role in the regulation of small nuclear RNA transcription that may affect neurodevelopment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, in the context of lung adenocarcinoma, a ceRNA network centered on ICE1 has been shown to enhance DNA damage induced by chemotherapeutic agents, suggesting its involvement in cancer cell chemosensitivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In plants, ICE1 homologs are well established as master regulators of cold stress tolerance. They activate C-repeat binding factors (CBFs) and downstream cold-responsive genes to promote freezing tolerance. In apple, for example, ICE1 interacts with other transcription factors such as MdBBX37"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "and MdABI4"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", thereby enhancing the expression of CBFs. ICE1 is also a strong candidate gene associated with winter survival traits in rye"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", and in poplar, overexpression of PsnICE1 improves cold tolerance through binding to specific stress-related promoter elements."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Similar ICE1-like genes in sweetpotato"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "and tea"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "reinforce a conserved role for ICE1 in activating the CBF pathway. Furthermore, redox-mediated modulation of ICE1 has been proposed to serve as a central hub integrating signals from both low temperature and light during cold acclimation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, ICE1 functions as a critical regulator in diverse biological systems. In mammalian cells, it is integral to RNA surveillance and transcription regulation, while in plants, its role as an activator of the CBF-dependent cold response underpins the development of freezing tolerance. These multifaceted activities underscore the evolutionary conservation and context-specific functionality of ICE1.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Thomas D Baird, Ken Chih-Chien Cheng, Yu-Chi Chen, et al. 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