{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T15:11:47Z","timestamp":1777993907052,"version":"3.51.4"},"reference-count":105,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,30]],"date-time":"2021-05-30T00:00:00Z","timestamp":1622332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["RTI2018-094629-B-I00"],"award-info":[{"award-number":["RTI2018-094629-B-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The Tribbles pseudokinases family consists of TRIB1, TRIB2, TRIB3 and STK40 and, although evolutionarily conserved, they have distinctive characteristics. Tribbles members are expressed in a context and cell compartment-dependent manner. For example, TRIB1 and TRIB2 have potent oncogenic activities in vertebrate cells. Since the identification of Tribbles proteins as modulators of multiple signalling pathways, recent studies have linked their expression with several pathologies, including cancer. Tribbles proteins act as protein adaptors involved in the ubiquitin-proteasome degradation system, as they bridge the gap between substrates and E3 ligases. Between TRIB family members, TRIB2 is the most ancestral member of the family. TRIB2 is involved in protein homeostasis regulation of C\/EBP\u03b1, \u03b2-catenin and TCF4. On the other hand, TRIB2 interacts with MAPKK, AKT and NFkB proteins, involved in cell survival, proliferation and immune response. Here, we review the characteristic features of TRIB2 structure and signalling and its role in many cancer subtypes with an emphasis on TRIB2 function in therapy resistance in melanoma, leukemia and glioblastoma. The strong evidence between TRIB2 expression and chemoresistance provides an attractive opportunity for targeting TRIB2.<\/jats:p>","DOI":"10.3390\/cancers13112701","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:22:15Z","timestamp":1622420535000},"page":"2701","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["The Critical Role of TRIB2 in Cancer and Therapy Resistance"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6972-2368","authenticated-orcid":false,"given":"Victor","family":"Mayoral-Varo","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d (CSIC-UAM), Arturo Duperier 4, 28029 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9576-1766","authenticated-orcid":false,"given":"Luc\u00eda","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d (CSIC-UAM), Arturo Duperier 4, 28029 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3340-5165","authenticated-orcid":false,"given":"Wolfgang","family":"Link","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d (CSIC-UAM), Arturo Duperier 4, 28029 Madrid, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S0092-8674(00)80861-2","article-title":"Tribbles Coordinates Mitosis and Morphogenesis in Drosophila by Regulating String\/CDC25 Proteolysis","volume":"101","author":"Mata","year":"2000","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4150","DOI":"10.1111\/febs.15246","article-title":"Cataloguing the dead: Breathing new life into pseudokinase research","volume":"287","author":"Shrestha","year":"2020","journal-title":"FEBS J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1111\/j.1349-7006.2011.01914.x","article-title":"Tribbles in disease: Signaling pathways important for cellular function and neoplastic transformation","volume":"102","author":"Yokoyama","year":"2011","journal-title":"Cancer Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.tcb.2016.11.002","article-title":"Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease","volume":"27","author":"Eyers","year":"2017","journal-title":"Trends Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1126\/science.1075762","article-title":"The protein kinase complement of the human genome","volume":"298","author":"Manning","year":"2002","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1042\/BST20150109","article-title":"Tribbles pseudokinases: Novel targets for chemical biology and drug discovery?","volume":"43","author":"Foulkes","year":"2015","journal-title":"Biochem. 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