Tuberin nuclear localization can be regulated by phosphorylation of its carboxyl terminus
- PMID: 17114346
- DOI: 10.1158/1541-7786.MCR-06-0056
Tuberin nuclear localization can be regulated by phosphorylation of its carboxyl terminus
Abstract
Tuberin, the tuberous sclerosis 2 (TSC2) gene product, has been identified as a tumor suppressor protein genetically implicated in the pathology of tuberous sclerosis and the female-specific lung disease lymphangioleiomyomatosis. Tuberin and its predominant cytoplasmic binding partner hamartin have been shown to complex with a variety of intracellular signaling regulators and affect the processes of protein translation, cellular proliferation, cellular migration, and cellular transcription. In previous studies, we have presented evidence for tuberin binding to the calcium-dependent intracellular signaling protein calmodulin (CaM), overlap of tuberin CaM binding domain with a binding domain for estrogen receptor alpha, and the phosphorylation-associated nuclear localization of tuberin. In the study presented here, we expand our findings on the mechanism of tuberin nuclear localization to show that the CaM-estrogen receptor-alpha binding domain of tuberin can also serve as a tuberin nuclear localization sequence. Furthermore, we identify an Akt/p90 ribosomal S6 kinase-1 phosphorylation site within the carboxyl terminus of tuberin that can regulate tuberin nuclear localization and significantly affect the ability of tuberin to modulate estrogen genomic signaling events. These findings suggest a link between tuberin nuclear localization and a variety of intracellular signaling events that have direct implications with respect to the role of tuberin in the pathology of tuberous sclerosis and lymphangioleiomyomatosis.
Similar articles
-
A calmodulin binding site in the tuberous sclerosis 2 gene product is essential for regulation of transcription events and is altered by mutations linked to tuberous sclerosis and lymphangioleiomyomatosis.Arch Biochem Biophys. 2002 Feb 1;398(1):132-40. doi: 10.1006/abbi.2001.2682. Arch Biochem Biophys. 2002. PMID: 11811958
-
Cytoplasmic/nuclear localization of tuberin in different cell lines.Amino Acids. 2007 Nov;33(4):575-9. doi: 10.1007/s00726-007-0541-0. Epub 2007 Apr 26. Amino Acids. 2007. PMID: 17458623
-
Akt regulates nuclear/cytoplasmic localization of tuberin.Oncogene. 2007 Jan 25;26(4):521-31. doi: 10.1038/sj.onc.1209812. Epub 2006 Jul 24. Oncogene. 2007. PMID: 16862180
-
The tuberous sclerosis gene products hamartin and tuberin are multifunctional proteins with a wide spectrum of interacting partners.Mutat Res. 2008 Mar-Apr;658(3):234-46. doi: 10.1016/j.mrrev.2008.01.001. Epub 2008 Jan 12. Mutat Res. 2008. PMID: 18291711 Review.
-
Tumour suppressors hamartin and tuberin: intracellular signalling.Cell Signal. 2003 Aug;15(8):729-39. doi: 10.1016/s0898-6568(03)00040-8. Cell Signal. 2003. PMID: 12781866 Review.
Cited by
-
New Insights into the Regulation of mTOR Signaling via Ca2+-Binding Proteins.Int J Mol Sci. 2023 Feb 15;24(4):3923. doi: 10.3390/ijms24043923. Int J Mol Sci. 2023. PMID: 36835331 Free PMC article. Review.
-
Dissecting the roles of the Tuberin protein in the subcellular localization of the G2/M Cyclin, Cyclin B1.PLoS One. 2022 Aug 10;17(8):e0272741. doi: 10.1371/journal.pone.0272741. eCollection 2022. PLoS One. 2022. PMID: 35947627 Free PMC article.
-
A Non-Canonical Calmodulin Target Motif Comprising a Polybasic Region and Lipidated Terminal Residue Regulates Localization.Int J Mol Sci. 2020 Apr 15;21(8):2751. doi: 10.3390/ijms21082751. Int J Mol Sci. 2020. PMID: 32326637 Free PMC article. Review.
-
mTOR Pathways in Cancer and Autophagy.Cancers (Basel). 2018 Jan 12;10(1):18. doi: 10.3390/cancers10010018. Cancers (Basel). 2018. PMID: 29329237 Free PMC article. Review.
-
A novel androgen-regulated isoform of the TSC2 tumour suppressor gene increases cell proliferation.Oncotarget. 2014 Jan 15;5(1):131-9. doi: 10.18632/oncotarget.1405. Oncotarget. 2014. PMID: 24318044 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous