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

Author

Listed:
  • Hyunjoo Kim

    (School of Biological Science/Bio-Max Institute, Seoul National University)

  • Ho-June Lee

    (Genentech, Inc. 1 DNA Way)

  • Yumin Oh

    (School of Biological Science/Bio-Max Institute, Seoul National University)

  • Seon-Guk Choi

    (School of Biological Science/Bio-Max Institute, Seoul National University)

  • Se-Hoon Hong

    (School of Biological Science/Bio-Max Institute, Seoul National University)

  • Hyo-Jin Kim

    (Genentech, Inc. 1 DNA Way)

  • Song-Yi Lee

    (School of Biological Science/Bio-Max Institute, Seoul National University)

  • Ji-Woo Choi

    (Center for Neuroscience, Korea Institute of Science and Technology)

  • Deog Su Hwang

    (School of Biological Science/Bio-Max Institute, Seoul National University)

  • Key-Sun Kim

    (Center for Neuroscience, Korea Institute of Science and Technology)

  • Hyo-Joon Kim

    (Hanyang University)

  • Jianke Zhang

    (Thomas Jefferson University)

  • Hyun-Jo Youn

    (Chonbuk National University Medical School)

  • Dong-Young Noh

    (Seoul National University College of Medicine)

  • Yong-Keun Jung

    (School of Biological Science/Bio-Max Institute, Seoul National University)

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-FADDSer194. 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-FADDSer191. 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.

Suggested Citation

  • 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 No, 2014. "The DUSP26 phosphatase activator adenylate kinase 2 regulates FADD phosphorylation and cell growth," Nature Communications, Nature, vol. 5(1), pages 1-11, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4351
    DOI: 10.1038/ncomms4351
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