N-terminal methionine excision of proteins creates tertiary destabilizing N-degrons of the Arg/N-end rule pathway.
N-end rule
N-terminal acetylation
N-terminal amidase
N-terminal arginylation
N-terminal methionine excision
acetylation
proteasome
protein degradation
ubiquitin
ubiquitin ligase
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
22 03 2019
22 03 2019
Historique:
received:
29
11
2018
revised:
18
01
2019
pubmed:
25
1
2019
medline:
18
12
2019
entrez:
25
1
2019
Statut:
ppublish
Résumé
All organisms begin protein synthesis with methionine (Met). The resulting initiator Met of nascent proteins is irreversibly processed by Met aminopeptidases (MetAPs). N-terminal (Nt) Met excision (NME) is an evolutionarily conserved and essential process operating on up to two-thirds of proteins. However, the universal function of NME remains largely unknown. MetAPs have a well-known processing preference for Nt-Met with Ala, Ser, Gly, Thr, Cys, Pro, or Val at position 2, but using CHX-chase assays to assess protein degradation in yeast cells, as well as protein-binding and RT-qPCR assays, we demonstrate here that NME also occurs on nascent proteins bearing Met-Asn or Met-Gln at their N termini. We found that the NME at these termini exposes the tertiary destabilizing Nt residues (Asn or Gln) of the Arg/N-end rule pathway, which degrades proteins according to the composition of their Nt residues. We also identified a yeast DNA repair protein, MQ-Rad16, bearing a Met-Gln N terminus, as well as a human tropomyosin-receptor kinase-fused gene (TFG) protein, MN-TFG, bearing a Met-Asn N terminus as physiological, MetAP-processed Arg/N-end rule substrates. Furthermore, we show that the loss of the components of the Arg/N-end rule pathway substantially suppresses the growth defects of
Identifiants
pubmed: 30674553
pii: S0021-9258(20)39018-9
doi: 10.1074/jbc.RA118.006913
pmc: PMC6433082
doi:
Substances chimiques
Proteins
0
Arginine
94ZLA3W45F
Methionine
AE28F7PNPL
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4464-4476Informations de copyright
© 2019 Nguyen et al.
Références
J Biol Chem. 1999 May 7;274(19):13403-9
pubmed: 10224104
Mol Biol Cell. 2013 Apr;24(7):890-900
pubmed: 23363603
Mol Cell Biol. 2005 Aug;25(16):7120-36
pubmed: 16055722
Science. 2017 Jan 27;355(6323):
pubmed: 28126757
Mol Cell Biol. 1995 Aug;15(8):4086-94
pubmed: 7623804
New Phytol. 2018 May;218(3):929-935
pubmed: 28581033
Science. 2018 Nov 30;362(6418):
pubmed: 30409808
Carcinogenesis. 2012 Aug;33(8):1450-8
pubmed: 22581839
Methods Mol Biol. 2014;1163:33-44
pubmed: 24841298
EMBO J. 2003 Jan 2;22(1):13-23
pubmed: 12505980
Oncotarget. 2016 Sep 27;7(39):63306-63323
pubmed: 27542228
Science. 1986 Oct 10;234(4773):179-86
pubmed: 3018930
Science. 2000 Sep 22;289(5487):2117-20
pubmed: 11000112
Trends Cell Biol. 2014 Oct;24(10):603-11
pubmed: 24874449
Science. 2015 Mar 13;347(6227):1249-1252
pubmed: 25766235
Biochemistry. 1988 Oct 18;27(21):7979-84
pubmed: 3069123
J Biol Chem. 2019 Jan 4;294(1):379-388
pubmed: 30425097
Cell. 2014 Jan 16;156(1-2):158-69
pubmed: 24361105
Nature. 2011 Oct 23;479(7373):419-22
pubmed: 22020282
Protein Sci. 2011 Aug;20(8):1298-345
pubmed: 21633985
Exp Mol Med. 2018 Jul 27;50(7):1-8
pubmed: 30054456
Nat Chem Biol. 2018 May;14(5):466-473
pubmed: 29632410
Mol Cell. 2014 Dec 4;56(5):630-40
pubmed: 25454947
Nat Cell Biol. 2010 Dec;12(12):1177-85
pubmed: 21076411
Biochim Biophys Acta. 2012 Jan;1823(1):83-91
pubmed: 21781991
Trends Pharmacol Sci. 2015 Nov;36(11):782-797
pubmed: 26434644
Microb Cell. 2015;2(10):376-393
pubmed: 26866044
Traffic. 2010 Oct;11(10):1363-9
pubmed: 20579315
Exp Mol Med. 2018 Jul 27;50(7):1-13
pubmed: 30054468
J Cell Physiol. 2006 Jul;208(1):154-60
pubmed: 16547966
Proc Natl Acad Sci U S A. 2017 Sep 12;114(37):E7707-E7716
pubmed: 28851831
J Biol Chem. 2006 Jan 6;281(1):392-400
pubmed: 16263705
Proteomics. 2008 Feb;8(4):626-49
pubmed: 18203265
Yeast. 2006 Oct-Nov;23(14-15):1053-64
pubmed: 17083136
Mol Cell. 2018 May 3;70(3):488-501.e5
pubmed: 29727619
Arch Biochem Biophys. 2002 Feb 1;398(1):87-93
pubmed: 11811952
Blood. 1999 Nov 1;94(9):3265-8
pubmed: 10556217
Proteomics. 2015 Jul;15(14):2436-46
pubmed: 25886145
Methods Enzymol. 2002;350:3-41
pubmed: 12073320
EMBO J. 1996 Sep 16;15(18):4884-99
pubmed: 8890162
Nat Cell Biol. 2015 Jul;17(7):917-29
pubmed: 26075355
Cell Cycle. 2014;13(9):1366-7
pubmed: 24698805
Annu Rev Biochem. 2012;81:261-89
pubmed: 22524314
Protein Pept Lett. 2016;23(4):343-8
pubmed: 26743630
Nature. 2000 Apr 13;404(6779):770-4
pubmed: 10783891
J Biol Chem. 2016 Aug 12;291(33):17178-96
pubmed: 27339900
Mol Cell Proteomics. 2013 Nov;12(11):3370-8
pubmed: 23897579
Mol Cell Proteomics. 2013 Jan;12(1):14-28
pubmed: 23001859
Nature. 2005 Oct 13;437(7061):981-6
pubmed: 16222293
Yeast. 1992 May;8(5):385-95
pubmed: 1626430
Mol Cell. 2013 May 23;50(4):540-51
pubmed: 23603116
FEBS Lett. 2008 May 14;582(11):1575-80
pubmed: 18407841
Nature. 2011 Oct 23;479(7373):415-8
pubmed: 22020279
Biochimie. 2015 Jul;114:134-46
pubmed: 25450248
Mol Cell. 2018 Mar 1;69(5):915
pubmed: 29499140
Science. 2010 Feb 19;327(5968):973-7
pubmed: 20110468
J Biol Chem. 2003 Aug 15;278(33):30686-97
pubmed: 12783868
Genes Chromosomes Cancer. 2004 Aug;40(4):325-8
pubmed: 15188455
Mol Cells. 2016 Mar;39(3):169-78
pubmed: 26883906
Plant Cell. 2015 May;27(5):1547-62
pubmed: 25966763
Proc Natl Acad Sci U S A. 2005 Oct 18;102(42):15030-5
pubmed: 16217033