The DUSP26 phosphatase activator adenylate kinase 2 regulates FADD phosphorylation and cell growth

Hyunjoo Kim, Ho June Lee, Yumin Oh, Seon Guk Choi, Se Hoon Hong, Hyo Jin Kim, Song Yi Lee, Ji Woo Choi, Deog Su Hwang, Key Sun Kim, Hyo Joon Kim, Jianke Zhang, Hyun Jo Youn, Dong Young Noh, Yong Keun Jung

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number3351
JournalNature communications
Volume5
DOIs
StatePublished - Feb 19 2014
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Kim, H., Lee, H. J., Oh, Y., Choi, S. G., Hong, S. H., Kim, H. J., Lee, S. Y., Choi, J. W., Su Hwang, D., Kim, K. S., Kim, H. J., Zhang, J., Youn, H. J., Noh, D. Y., & Jung, Y. K. (2014). The DUSP26 phosphatase activator adenylate kinase 2 regulates FADD phosphorylation and cell growth. Nature communications, 5, [3351]. https://doi.org/10.1038/ncomms4351