Format

Send to

Choose Destination
Nat Commun. 2014;5:3351. doi: 10.1038/ncomms4351.

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

Author information

1
1] School of Biological Science/Bio-Max Institute, Seoul National University, Gwanak-gu, Seoul 151-747, Korea [2].
2
1] Department of Discovery Oncology, Genentech, Inc. 1 DNA Way, South San Francisco, California 94080, USA [2].
3
School of Biological Science/Bio-Max Institute, Seoul National University, Gwanak-gu, Seoul 151-747, Korea.
4
Department of Discovery Oncology, Genentech, Inc. 1 DNA Way, South San Francisco, California 94080, USA.
5
Center for Neuroscience, Korea Institute of Science and Technology, Seoul 136-791, Korea.
6
Department of Biochemistry, Hanyang University, Ansan, Kyeonggi-do 425-791, Korea.
7
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
8
Department of Surgery, Chonbuk National University Medical School, Jeonju 561-180, Korea.
9
Department of Surgery, Seoul National University College of Medicine, Seoul 110-744, Korea.

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.

PMID:
24548998
PMCID:
PMC3948464
DOI:
10.1038/ncomms4351
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center