eEF2K as an important kinase associated with cancer survival and prognosis
Eukaryotic Elongation Factor 2 Kinase (eEF2K), a member of the α-kinase family, services as a crucial negative regulator of protein synthesis, particularly under conditions of cellular stress. A pan-cancer analysis of eEF2K expression, genetic variants, and clinical relevance across multiple tumor types was performed using data from the Cancer Genome Atlas (TCGA) and GEO. Our findings suggest that eEF2K has dual roles in cancer progression, with its expression correlating with patient prognosis. Significant phosphorylation of eEF2 at T57, Y434, and T59 was observed, which may regulate protein synthesis during stress. The elevated T59 phosphorylation in COAD, despite the low eEF2K expression, indicates that this may be regulated by alternative kinases, such as AMPK or mTOR. This suggests that compensatory mechanisms may be involved. In addition to modulating eEF2 phosphorylation, eEF2K is involved in a number of other processes, including peptidyl-serine phosphorylation, the G2/M transition, and the MAPK cascade. The protein products of eEF2K are capable of localizing to the nucleus, cytoplasm, and cytosol, where they bind to a range of proteins, including ATP and calcium ions. These findings provide novel insights into the role of eEF2K in cancer biology and suggest that the targeting of eEF2K and eEF2 phosphorylation may offer promising therapeutic strategies.
Authors
- Qian Yang (ORCID: https://orcid.org/0000-0003-1969-0390)
- Lucas Liu
- Xinhong Zhou
- Xi‐Dai Long (ORCID: https://orcid.org/0000-0003-0960-0689)
- Yihe Zhang (ORCID: https://orcid.org/0000-0003-2814-2724)
- Lilan Cen (ORCID: https://orcid.org/0000-0003-1876-129X)
- Nan Wang (ORCID: https://orcid.org/0000-0002-9066-2790)
- Jun Zhang (ORCID: https://orcid.org/0000-0001-7886-6187)
- Di Yang (ORCID: https://orcid.org/0000-0003-3915-523X)
- Yongzhi Huang (ORCID: https://orcid.org/0000-0002-5545-5307)
- Qian Gu (ORCID: https://orcid.org/0000-0002-7394-5238)
- Z. F. Tian (ORCID: https://orcid.org/0009-0007-9890-5922)
- Miao-Miao An
Institutions
- Atrium Health Wake Forest Baptist (US)
- Atkins (United States) (US)
- Peking University (CN)
- Nankai University (CN)
- Tianjin Medical University Cancer Institute and Hospital (CN)
- The People's Hospital of Guangxi Zhuang Autonomous Region (CN)
- Affiliated Hospital of Youjiang Medical University for Nationalities (CN)
- Peking University International Hospital (CN)
- Wake Forest Baptist Comprehensive Cancer Center
Publication Details
- Journal
- Scientific Reports
- Published
- 2024-11-26
- DOI
- https://doi.org/10.1038/s41598-024-78652-4
- Citations
- 7
- Primary Topic
- Advanced Proteomics Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 1.69
Funders
- Natural Science Foundation of Guangxi Zhuang Autonomous Region
- Natural Science Foundation of Guangxi Province
- Tianjin Medical University
- Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Division of Graduate Education