Stability of tuberous sclerosis complex 2 is controlled by methylation at R1457 and R1459.
Arginine
/ metabolism
HEK293 Cells
HeLa Cells
Humans
Methylation
Phosphorylation
Phosphothreonine
/ metabolism
Protein Binding
Protein Stability
Protein-Arginine N-Methyltransferases
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Repressor Proteins
/ metabolism
Tuberous Sclerosis Complex 2 Protein
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
03 12 2020
03 12 2020
Historique:
received:
20
04
2020
accepted:
23
11
2020
entrez:
4
12
2020
pubmed:
5
12
2020
medline:
17
3
2021
Statut:
epublish
Résumé
Mutations in genes that encode components of tuberous sclerosis complex 2 (TSC2) are associated with tuberous sclerosis complex disease. TSC2 interacts with tuberous sclerosis complex 1 to form a complex that negatively regulates cell growth and proliferation via the inactivation of mechanistic target of rapamycin complex 1. The activity of TSC2 is mainly regulated via posttranslational modifications such as phosphorylation. However, the control of TSC2 activity is not entirely achieved by phosphorylation. In this study, we show that TSC2 is methylated at R1457 and R1459 by protein arginine methyltransferase 1 (PRMT1). Methylation of these two residues can affect the phosphorylation status through protein kinase B (Akt) of TSC2 at T1462 and is essential for TSC2 stability. Taken together, these findings indicate that novel posttranslational modifications are important for the regulation of TSC2 stability through PRMT1-mediated methylation.
Identifiants
pubmed: 33273660
doi: 10.1038/s41598-020-78274-6
pii: 10.1038/s41598-020-78274-6
pmc: PMC7713242
doi:
Substances chimiques
Repressor Proteins
0
Tuberous Sclerosis Complex 2 Protein
0
Phosphothreonine
1114-81-4
Arginine
94ZLA3W45F
PRMT1 protein, human
EC 2.1.1.319
Protein-Arginine N-Methyltransferases
EC 2.1.1.319
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
21160Références
Arch Biochem Biophys. 2016 Jan 15;590:138-152
pubmed: 26612103
J Cell Biol. 2006 Apr 24;173(2):279-89
pubmed: 16636147
Biochemistry. 2008 Sep 9;47(36):9456-66
pubmed: 18700728
J Biol Chem. 1992 Feb 15;267(5):2864-7
pubmed: 1346611
Mol Cell. 2017 Jan 5;65(1):8-24
pubmed: 28061334
J Biol Chem. 2013 Nov 15;288(46):33016-26
pubmed: 24089531
Cell Stem Cell. 2012 Sep 7;11(3):333-45
pubmed: 22863532
Cell Metab. 2014 May 6;19(5):780-94
pubmed: 24746804
Cell. 2014 Feb 13;156(4):771-85
pubmed: 24529379
J Biol Chem. 1997 Mar 7;272(10):6097-100
pubmed: 9045618
Biochem J. 2008 Jun 1;412(2):179-90
pubmed: 18466115
Cell Metab. 2017 Feb 7;25(2):463-471
pubmed: 28089566
Biochim Biophys Acta. 2002 Aug 19;1591(1-3):1-10
pubmed: 12183049
Biochem Biophys Res Commun. 2008 Mar 28;368(1):132-7
pubmed: 18230340
J Biol Chem. 2002 Sep 20;277(38):35364-70
pubmed: 12167664
Oncogene. 2002 Dec 5;21(55):8470-6
pubmed: 12466966
Sci Rep. 2016 Feb 19;6:21807
pubmed: 26892894
Nutrients. 2020 Mar 03;12(3):
pubmed: 32138282
Mol Cell Biol. 2004 Sep;24(18):7965-75
pubmed: 15340059
PLoS One. 2009 Jul 10;4(7):e6189
pubmed: 19593385
Mol Cell. 2009 Jan 16;33(1):1-13
pubmed: 19150423
J Biol Chem. 2004 Jun 4;279(23):23892-9
pubmed: 15056663
Nat Cell Biol. 2003 Jun;5(6):566-71
pubmed: 12766776
Nat Cell Biol. 2002 Sep;4(9):648-57
pubmed: 12172553
Genes Dev. 2005 Aug 15;19(16):1885-93
pubmed: 16103216
Cell. 2017 Apr 20;169(3):381-405
pubmed: 28431241
Cell. 2003 Nov 26;115(5):577-90
pubmed: 14651849
FEBS Lett. 2020 Jan;594(2):301-316
pubmed: 31541584
Genes Dev. 2003 Aug 1;17(15):1829-34
pubmed: 12869586
Nat Rev Dis Primers. 2016 May 26;2:16035
pubmed: 27226234
Sci Rep. 2016 Jun 24;6:28718
pubmed: 27338245
J Biol Chem. 2003 Apr 4;278(14):12361-6
pubmed: 12517744
Mol Cell. 2013 Jun 6;50(5):613-23
pubmed: 23746349
Arch Biochem Biophys. 2016 Jan 15;590:48-55
pubmed: 26550928
Mol Cell. 2002 Jul;10(1):151-62
pubmed: 12150915
Mol Cell. 2008 Oct 24;32(2):221-31
pubmed: 18951090
J Nutrigenet Nutrigenomics. 2009;2(1):29-36
pubmed: 19776636
Hum Mol Genet. 1998 Jun;7(6):1053-7
pubmed: 9580671