{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough the query mentions MROH2B, none of the provided abstracts describe its function. Instead, the literature details the multifaceted roles of eukaryotic elongation factor 2 kinase (eEF2K) – a pivotal regulator of protein synthesis. eEF2K governs translation elongation by phosphorylating its sole substrate, eEF2, a modification that slows global protein synthesis and conserves cellular energy under stress. In conditions such as nutrient deprivation, hypoxia, and endoplasmic reticulum stress, eEF2K is activated (thereby also modulating autophagy and stress‐induced signaling), a process that underpins cell survival and, in many tumors, contributes to metabolic adaptation and chemoresistance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the nervous system, eEF2K critically influences synaptic function and plasticity. Its activity regulates the balance between excitatory and inhibitory transmission – for instance, by modulating levels of presynaptic proteins and GABAA receptors – thereby affecting memory consolidation and neuronal excitability. In addition, aberrant eEF2K signaling has been linked to neurodegenerative conditions such as Alzheimer’s disease, where excessive eEF2 phosphorylation contributes to deficits in synaptic plasticity. Proteomic studies further suggest that eEF2K’s regulation of translation elongation may fine‐tune the synthesis of microtubule‐related proteins, potentially impacting cytoskeletal dynamics in neurons."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond neuronal regulation, eEF2K plays key roles in diverse physiological and pathological contexts. In germ cells, it helps maintain oocyte quality by promoting the rapid downregulation of short‐lived antiapoptotic proteins, thereby eliminating defective cells. In the vasculature and immune system, eEF2K influences smooth muscle cell proliferation, macrophage foam cell formation, and T cell as well as natural killer cell function, linking its activity to processes such as hypertension, atherosclerosis, and tumor immune evasion. Moreover, under conditions of acidosis or genotoxic stress, eEF2K controls cell cycle arrest to prevent mitotic catastrophe, highlighting its overall contribution to cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Suvi P Kallio, Eveliina Jakkula, Shaun Purcell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Use of a genetic isolate to identify rare disease variants: C7 on 5p associated with MS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddp073"}], "href": "https://doi.org/10.1093/hmg/ddp073"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19221116"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19221116"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Bénédicte F Py, Michael Boyce, Junying Yuan "}, {"type": "b", "children": [{"type": "t", "text": "A critical role of eEF-2K in mediating autophagy in response to multiple cellular stresses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/auto.5.3.7762"}], "href": "https://doi.org/10.4161/auto.5.3.7762"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19221463"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19221463"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Aslam A Khan, Dru S Dace, Alexey G Ryazanov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Resveratrol regulates pathologic angiogenesis by a eukaryotic elongation factor-2 kinase-regulated pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2353/ajpath.2010.090836"}], "href": "https://doi.org/10.2353/ajpath.2010.090836"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20472894"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20472894"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Gabriel Leprivier, Marc Remke, Barak Rotblat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2013.04.055"}], "href": "https://doi.org/10.1016/j.cell.2013.04.055"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23706743"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23706743"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Claire E J Moore, Halina Mikolajek, Sergio Regufe da Mota, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elongation Factor 2 Kinase Is Regulated by Proline Hydroxylation and Protects Cells during Hypoxia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01457-14"}], "href": "https://doi.org/10.1128/MCB.01457-14"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25755286"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25755286"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Claire E J Moore, Xuemin Wang, Jianling Xie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elongation factor 2 kinase promotes cell survival by inhibiting protein synthesis without inducing autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2016.01.005"}], "href": "https://doi.org/10.1016/j.cellsig.2016.01.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26795954"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26795954"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "M Johanns, S Pyr Dit Ruys, A Houddane, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Direct and indirect activation of eukaryotic elongation factor 2 kinase by AMP-activated protein kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2017.05.010"}], "href": "https://doi.org/10.1016/j.cellsig.2017.05.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28502587"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28502587"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Iness Gildish, David Manor, Orit David, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impaired associative taste learning and abnormal brain activation in kinase-defective eEF2K mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Learn Mem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/lm.023937.111"}], "href": "https://doi.org/10.1101/lm.023937.111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22366775"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22366775"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Justin W Kenney, Maja Genheden, Kyung-Mee Moon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Eukaryotic elongation factor 2 kinase regulates the synthesis of microtubule-related proteins in neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jnc.13407"}], "href": "https://doi.org/10.1111/jnc.13407"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26485687"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26485687"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Christopher Heise, Elham Taha, Luca Murru, et al. "}, {"type": "b", "children": [{"type": "t", "text": "eEF2K/eEF2 Pathway Controls the Excitation/Inhibition Balance and Susceptibility to Epileptic Seizures."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cereb Cortex (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/cercor/bhw075"}], "href": "https://doi.org/10.1093/cercor/bhw075"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27005990"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27005990"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Asad Jan, Brandon Jansonius, Alberto Delaidelli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "eEF2K inhibition blocks Aβ42 neurotoxicity by promoting an NRF2 antioxidant response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00401-016-1634-1"}], "href": "https://doi.org/10.1007/s00401-016-1634-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27752775"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27752775"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Patrick R Smith, Sarah Loerch, Nikesh Kunder, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functionally distinct roles for eEF2K in the control of ribosome availability and p-body abundance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-27160-4"}], "href": "https://doi.org/10.1038/s41467-021-27160-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34815424"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34815424"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Hsueh-Ping Chu, Yi Liao, James S Novak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Germline quality control: eEF2K stands guard to eliminate defective oocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2014.01.027"}], "href": "https://doi.org/10.1016/j.devcel.2014.01.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24582807"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24582807"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "T Usui, R Nijima, T Sakatsume, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Eukaryotic elongation factor 2 kinase controls proliferation and migration of vascular smooth muscle cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Physiol (Oxf) (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/apha.12354"}], "href": "https://doi.org/10.1111/apha.12354"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25069823"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25069823"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Jianling Xie, Halina Mikolajek, Craig R Pigott, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular Mechanism for the Control of Eukaryotic Elongation Factor 2 Kinase by pH: Role in Cancer Cell Survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00012-15"}], "href": "https://doi.org/10.1128/MCB.00012-15"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25776553"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25776553"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Sanuja Fernando, Thalia Salagaras, Nisha Schwarz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Eukaryotic elongation factor 2 kinase regulates foam cell formation via translation of CD36."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.202101034R"}], "href": "https://doi.org/10.1096/fj.202101034R"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35032419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35032419"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Jugal Kishore Das, Yijie Ren, Anil Kumar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elongation factor-2 kinase is a critical determinant of the fate and antitumor immunity of CD8"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Adv (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/sciadv.abl9783"}], "href": "https://doi.org/10.1126/sciadv.abl9783"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35108044"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35108044"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Chao-Qun Qin, Bin Huang, Fang Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Effects of GSK3β/eEF2K signaling pathway on pulmonary fibrosis in mice]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhongguo Ying Yong Sheng Li Xue Za Zhi (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.12047/j.cjap.6201.2022.006"}], "href": "https://doi.org/10.12047/j.cjap.6201.2022.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35634666"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35634666"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Yan Xu, Fang Sun, Yuying Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Enhanced NK cell activation via eEF2K-mediated potentiation of the cGAS-STING pathway in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Immunopharmacol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.intimp.2024.111628"}], "href": "https://doi.org/10.1016/j.intimp.2024.111628"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38320351"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38320351"}]}]}]}