{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T06:04:21Z","timestamp":1792821861590,"version":"4.5.0"},"reference-count":122,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T00:00:00Z","timestamp":1735344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>S6 Kinase 2 (S6K2) is a key regulator of cellular signaling and is crucial for cell growth, proliferation, and survival. This review is divided into two parts: the first focuses on the complex network of upstream effectors, downstream modulators, and post-translational modifications (PTMs) that regulate S6K2 activity. We emphasize the dynamic nature of S6K2 regulation, highlighting its critical role in cellular homeostasis and its potential as a therapeutic target in diseases like cancer. The second part utilizes in silico analyses, employing computational tools to model S6K2\u2019s three-dimensional structure and predict its interaction networks. Molecular dynamics simulations and docking studies reveal potential binding sites and interactions with novel known inhibitors. We also examine the effects of environmental contaminants that potentially disrupt S6K2 function and provide insights into the role of external factors that could impact its regulatory mechanisms. These computational findings provide a deeper understanding of the conformational dynamics of S6K2 and its interactions with its inhibitors. Together, this integrated biochemical and computational approach enhances our understanding of S6K2 regulation and identifies potential new therapeutic strategies targeting S6K2 in the oncology setting.<\/jats:p>","DOI":"10.3390\/ijms26010176","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T07:34:19Z","timestamp":1735630459000},"page":"176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["S6K2 in Focus: Signaling Pathways, Post-Translational Modifications, and Computational Analysis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7629-4357","authenticated-orcid":false,"given":"Mahmoud I.","family":"Khalil","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Faculty of Sciences, Beirut Arab University, Beirut P.O. Box 11-5020, Lebanon"},{"name":"Molecular Biology Unit, Department of Zoology, Faculty of Science, Alexandria University, Alexandria 21568, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6170-4907","authenticated-orcid":false,"given":"Mohamed","family":"Helal","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Southern Denmark, 5230 Odense, Denmark"},{"name":"National Institute of Oceanography and Fisheries (NIOF), Cairo 11516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5312-4870","authenticated-orcid":false,"given":"Ahmed F.","family":"El-Sayed","sequence":"additional","affiliation":[{"name":"Microbial Genetics Department, Biotechnology Research Institute, National Research Centre, Giza 12622, Egypt"},{"name":"Egypt Center for Research and Regenerative Medicine (ECRRM), Cairo 11517, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9125-5137","authenticated-orcid":false,"given":"Rana","family":"El Hajj","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Sciences, Beirut Arab University, Beirut P.O. Box 11-5020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7743-6740","authenticated-orcid":false,"given":"Jasmine","family":"Holail","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"},{"name":"Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol BS1 3NY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Houssein","sequence":"additional","affiliation":[{"name":"Scientific Support, HVD Life Sciences, Riyadh 11411, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4635-021X","authenticated-orcid":false,"given":"Ahmed","family":"Waraky","sequence":"additional","affiliation":[{"name":"Region V\u00e4stra G\u00f6taland, Department of Clinical Chemistry, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden"},{"name":"Department of Haematology, Cambridge Stem Cell Institute, Cambridge University, Cambridge CB20AW, UK"},{"name":"Department of Laboratory Medicine, University of Gothenburg, 41345 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2223-1435","authenticated-orcid":false,"given":"Olivier E.","family":"Pardo","sequence":"additional","affiliation":[{"name":"Division of Cancer, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gerstenecker, S., Haarer, L., Schroder, M., Kudolo, M., Schwalm, M.P., Wydra, V., Serafim, R.A.M., Chaikuad, A., Knapp, S., and Laufer, S. 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