The tuberous sclerosis gene products hamartin and tuberin are multifunctional proteins with a wide spectrum of interacting partners
Abstract
Mutations in the tumor suppressor genes TSC1 and TSC2, encoding hamartin and tuberin, respectively, cause the tumor syndrome tuberous sclerosis with similar phenotypes. Until now, over 50 proteins have been demonstrated to interact with hamartin and/or tuberin. Besides tuberin, the proteins DOCK7, ezrin/radixin/moesin, FIP200, IKKβ, Melted, Merlin, NADE(p75NTR), NF-L, Plk1 and TBC7 have been found to interact with hamartin. Whereas Plk1 and TBC7 have been demonstrated not to bind to tuberin, for all the other hamartin-interacting proteins the question, whether they can also bind to tuberin, has not been studied. Tuberin interacts with 14-3-3 β,ɛ,γ,η,σ,τ,ζ, Akt, AMPK, CaM, CRB3/PATJ, cyclin A, cyclins D1, D2, D3, Dsh, ERα, Erk, FoxO1, HERC1, HPV16 E6, HSCP-70, HSP70-1, MK2, NEK1, p27 KIP1, Pam, PC1, PP2Ac, Rabaptin-5, Rheb, RxRα/VDR and SMAD2/3. 14-3-3 β,ɛ,γ,η,σ,τ,ζ, Akt, Dsh, FoxO1, HERC1, p27 KIP1 and PP2Ac are known not to bind to hamartin. For the other tuberin-interacting proteins this question remains elusive. The proteins axin, Cdk1, cyclin B1, GADD34, GSK3, mTOR and RSK1 have been found to co-immunoprecipitate with both, hamartin and tuberin. The kinases Cdk1 and IKKβ phosphorylate hamartin, Erk, Akt, MK2, AMPK and RSK1 phosphorylate tuberin, and GSK3 phosphorylates both, hamartin and tuberin. This detailed summary of protein interactions allows new insights into their relevance for the wide variety of different functions of hamartin and tuberin.
- Publication:
-
Mutation Research - Reviews in Mutation Research
- Pub Date:
- January 2008
- DOI:
- 10.1016/j.mrrev.2008.01.001
- Bibcode:
- 2008MRRMR.658..234R
- Keywords:
-
- aa;
- amino acid;
- GAP;
- GTPase-activating protein;
- GST;
- glutathione-S-transferase;
- IP;
- immunoprecipitation;
- MALDI-TOF MS;
- matrix assisted laser desorption ionization-time of flight mass spectrometry;
- TSC;
- tuberous sclerosis;
- TSC1;
- tuberous sclerosis gene 1;
- TSC2;
- tuberous sclerosis gene 2;
- Y2H;
- yeast-two-hybrid assay;
- Hamartin;
- Protein interaction;
- TSC1;
- TSC2;
- Tuberin;
- Tuberous sclerosis