Kim, Hyunjoo Lee, Ho-June Oh, Yumin Choi, Seon-Guk Hong, Se-Hoon Kim, Hyo-Jin Lee, Song-Yi Choi, Ji-Woo Hwang, Deog Su Kim, Key-Sun Kim, Hyo-Joon Zhang, Jianke Youn, Hyun-Jo Noh, Dong-Young Jung, Yong-Keun 2024-01-20T10:32:31Z 2024-01-20T10:32:31Z 2021-09-05 2014-02 2041-1723 https://pubs.kist.re.kr/handle/201004/127163 Adenylate kinase 2 (AK2), which balances adenine nucleotide pool, is a multi-functional protein. Here we show that AK2 negatively regulates tumour cell growth. AK2 forms a complex with dual-specificity phosphatase 26 (DUSP26) phosphatase and stimulates DUSP26 activity independently of its AK activity. AK2/DUSP26 phosphatase protein complex dephosphorylates fas-associated protein with death domain (FADD) and regulates cell growth. AK2 deficiency enhances cell proliferation and induces tumour formation in a xenograft assay. This anti-growth function of AK2 is associated with its DUSP26-stimulating activity. Downregulation of AK2 is frequently found in tumour cells and human cancer tissues showing high levels of phospho-FADD(Ser194). Moreover, reconstitution of AK2 in AK2-deficient tumour cells retards both cell proliferation and tumourigenesis. Consistent with this, AK2(+/-) mouse embryo fibroblasts exhibit enhanced cell proliferation with a significant alteration in phospho-FADD(Ser191). These results suggest that AK2 is an associated activator of DUSP26 and suppresses cell proliferation by FADD dephosphorylation, postulating AK2 as a negative regulator of tumour growth. English NATURE PUBLISHING GROUP The DUSP26 phosphatase activator adenylate kinase 2 regulates FADD phosphorylation and cell growth Article 10.1038/ncomms4351 1 NATURE COMMUNICATIONS, v.5 NATURE COMMUNICATIONS 5 N scie scopus 000332669600006 2-s2.0-84894597311 Multidisciplinary Sciences Science & Technology - Other Topics Article ASSOCIATION EXPRESSION INHIBITOR DEATH DOMAIN PROTEIN FAS-MEDIATED APOPTOSIS CHROMOSOME ARM 8P NF-KAPPA-B PROTEOMIC ANALYSIS CYCLE CANCER Apoptosis Adenylate kinase 2 FADD DUSP26