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Molecular and Cellular Biology, July 2009, p. 3569-3581, Vol. 29, No. 13
0270-7306/09/$08.00+0     doi:10.1128/MCB.01909-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Knockdown of Human N{alpha}-Terminal Acetyltransferase Complex C Leads to p53-Dependent Apoptosis and Aberrant Human Arl8b Localization{triangledown}

Kristian K. Starheim,1,2,3 Darina Gromyko,1,2,3 Rune Evjenth,1 Anita Ryningen,4 Jan Erik Varhaug,2,3 Johan R. Lillehaug,1 and Thomas Arnesen1,2,3*

Department of Molecular Biology, University of Bergen, N-5020 Bergen, Norway,1 Department of Surgical Sciences, University of Bergen, N-5020 Bergen, Norway,2 Department of Surgery, Haukeland University Hospital, N-5021 Bergen, Norway,3 Department of Medicine, Haukeland University Hospital, N-5021 Bergen, Norway4

Received 18 December 2008/ Returned for modification 19 February 2009/ Accepted 18 April 2009

Protein N{alpha}-terminal acetylation is one of the most common protein modifications in eukaryotic cells. In yeast, three major complexes, NatA, NatB, and NatC, catalyze nearly all N-terminal acetylation, acetylating specific subsets of protein N termini. In human cells, only the NatA and NatB complexes have been described. We here identify and characterize the human NatC (hNatC) complex, containing the catalytic subunit hMak3 and the auxiliary subunits hMak10 and hMak31. This complex associates with ribosomes, and hMak3 acetylates Met-Leu protein N termini in vitro, suggesting a model in which the human NatC complex functions in cotranslational N-terminal acetylation. Small interfering RNA-mediated knockdown of NatC subunits results in p53-dependent cell death and reduced growth of human cell lines. As a consequence of hMAK3 knockdown, p53 is stabilized and phosphorylated and there is a significant transcriptional activation of proapoptotic genes downstream of p53. Knockdown of hMAK3 alters the subcellular localization of the Arf-like GTPase hArl8b, supporting that hArl8b is a hMak3 substrate in vivo. Taken together, hNatC-mediated N-terminal acetylation is important for maintenance of protein function and cell viability in human cells.

* Corresponding author. Mailing address: Department of Molecular Biology, University of Bergen, Thormøhlensgate 55, N-5020 Bergen, Norway. Phone: 47 55584539. Fax: 47 55589683. E-mail: Thomas.Arnesen{at}mbi.uib.no

{triangledown} Published ahead of print on 27 April 2009.

Molecular and Cellular Biology, July 2009, p. 3569-3581, Vol. 29, No. 13
0270-7306/09/$08.00+0     doi:10.1128/MCB.01909-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Evjenth, R., Hole, K., Karlsen, O. A., Ziegler, M., Arnesen, T., Lillehaug, J. R. (2009). Human Naa50p (Nat5/San) Displays Both Protein N{alpha}- and N{epsilon}-Acetyltransferase Activity. J. Biol. Chem. 284: 31122-31129 [Abstract] [Full Text]  


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