{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T16:35:30Z","timestamp":1783528530086,"version":"3.55.0"},"reference-count":33,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2012,7,5]],"date-time":"2012-07-05T00:00:00Z","timestamp":1341446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2012,8]]},"abstract":"Erythroid differentiation\u2010associated gene (EDAG) is a haematopoietic tissue\u2010specific transcription regulator that plays a key role in maintaining the homeostasis of haematopoietic lineage commitment. In acute myeloid leukaemia (AML) patients, the high expression level of EDAG is associated with poor prognosis. NPM1 (nucleophosmin\/B23), a ubiquitous nucleolar phosphoprotein, comprises a multifunctional protein that is involved in several cellular processes, including ribosome biogenesis, centrosome duplication, cell cycle progression, cell growth and transformation. Various studies have implicated NPM1 overexpression in promoting tumour cell proliferation, blocking the differentiation of leukaemia cells and resisting apoptosis. In the present study, using co\u2010immunoprecipitation, we characterized EDAG as a physiological binding partner of NPM1; The N\u2010terminal (amino acids 1\u2013124) region of EDAG interacts with the N\u2010terminal (amino acids 118\u2013187) of NPM1. Under cycloheximide treatment, the stability of NPM1 protein was enhanced by EDAG overexpression, whereas knockdown of EDAG by lentivirus\u2010mediated small interfering RNA resulted in an increased degradation rate of NPM1 in K562 cells. During 4\u03b2\u2010phorbol l2\u2010myristate 13\u2010acetate\u2010induced K562 megakaryocytic differentiation, overexpression of EDAG prevented the down\u2010regulation of NPM1 proteins, whereas knockdown of EDAG accelerated the down\u2010regulation of NPM1. EDAG deletion mutant lacking the binding domain with NPM1 lost the ability to stabilize NPM1 protein. Furthermore, knockdown of EDAG in K562 cells led to increased cell apoptosis induced by imatinib, and re\u2010expression of NPM1 attenuated the increased apoptosis. These results suggest that EDAG enhances the protein stability of NPM1 via binding to NPM1, which plays a critical role in the anti\u2010apoptosis of leukaemia cells.<\/jats:p>Structured digital abstract<\/jats:bold><\/jats:p>\n\u2002NPM1<\/jats:ext-link>\u2003physically interacts<\/jats:ext-link>\u2003with\u2003EDAG<\/jats:ext-link>\u2003by\u2003anti bait coimmunoprecipitation<\/jats:ext-link>\u2003(View interaction<\/jats:ext-link>)<\/jats:p><\/jats:list-item>\n\u2002EDAG<\/jats:ext-link>\u2003physically interacts<\/jats:ext-link>\u2003with\u2003HSPA1A<\/jats:ext-link>,\u2003UBTF<\/jats:ext-link>,\u2003SP100<\/jats:ext-link>,\u2003NPM1<\/jats:ext-link>,\u2003HNRPA3<\/jats:ext-link>,\u2003MCM3<\/jats:ext-link>\u2003,UBE1<\/jats:ext-link>,\u2003FBL<\/jats:ext-link>,\u2003ZnF20<\/jats:ext-link>,\u2003ZnF25<\/jats:ext-link>\u2003and\u2003MNDA<\/jats:ext-link>\u2003by\u2003anti bait coimmunoprecipitation<\/jats:ext-link>\u2003(View interaction<\/jats:ext-link>)<\/jats:p><\/jats:list-item>\n\u2002EDAG<\/jats:ext-link>\u2003physically interacts<\/jats:ext-link>\u2003with\u2003NPM1<\/jats:ext-link>\u2003by\u2003anti tag coimmunoprecipitation<\/jats:ext-link>\u2003(View Interaction:\u20031<\/jats:ext-link>,\u20032<\/jats:ext-link>,\u20033<\/jats:ext-link>)<\/jats:p><\/jats:list-item>\n\u2002EDAG<\/jats:ext-link>\u2003and\u2003NPM1<\/jats:ext-link>\u2003colocalize<\/jats:ext-link>\u2003by\u2003fluorescence microscopy<\/jats:ext-link>\u2003(View Interaction:\u20031<\/jats:ext-link>,\u20032<\/jats:ext-link>)<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p>","DOI":"10.1111\/j.1742-4658.2012.08663.x","type":"journal-article","created":{"date-parts":[[2012,6,19]],"date-time":"2012-06-19T16:41:56Z","timestamp":1340124116000},"page":"2848-2862","source":"Crossref","is-referenced-by-count":13,"title":["Erythroid differentiation\u2010associated gene interacts with NPM1 (nucleophosmin\/B23) and increases its protein 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