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PMID: 18466115 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

The TSC1-TSC2 complex: a molecular switchboard controlling cell growth.

The Biochemical journal ·Vol. 412 ·No. 2 ·2008-06-01 ·Pages 179-90

Huang J, Manning BD

Abstract

TSC1 and TSC2 are the tumour-suppressor genes mutated in the tumour syndrome TSC (tuberous sclerosis complex). Their gene products form a complex that has become the focus of many signal transduction researchers. The TSC1-TSC2 (hamartin-tuberin) complex, through its GAP (GTPase-activating protein) activity towards the small G-protein Rheb (Ras homologue enriched in brain), is a critical negative regulator of mTORC1 (mammalian target of rapamycin complex 1). As mTORC1 activity controls anabolic processes to promote cell growth, it is exquisitely sensitive to alterations in cell growth conditions. Through numerous phosphorylation events, the TSC1-TSC2 complex has emerged as the sensor and integrator of these growth conditions, relaying signals from diverse cellular pathways to properly modulate mTORC1 activity. In the present review we focus on the molecular details of TSC1-TSC2 complex regulation and function as it relates to the control of Rheb and mTORC1.

MeSH Terms
Amino Acid Sequence Animals Cell Cycle/physiology Cell Growth Processes Genes, Tumor Suppressor Humans Insulin/metabolism Insulin-Like Growth Factor I/genetics,metabolism Intercellular Signaling Peptides and Proteins/metabolism Molecular Sequence Data Monomeric GTP-Binding Proteins/genetics,metabolism Neuropeptides/genetics,metabolism Protein Kinases/genetics,metabolism Ras Homolog Enriched in Brain Protein Ribosomal Protein S6 Kinases/genetics,metabolism Sequence Alignment Signal Transduction/physiology TOR Serine-Threonine Kinases Transcription Factors/genetics,metabolism Tuberous Sclerosis Complex 1 Protein Tuberous Sclerosis Complex 2 Protein Tumor Suppressor Proteins/genetics,metabolism
Chemicals
CRTC1 protein, human Insulin Intercellular Signaling Peptides and Proteins Neuropeptides RHEB protein, human Ras Homolog Enriched in Brain Protein TSC1 protein, human TSC2 protein, human Transcription Factors Tuberous Sclerosis Complex 1 Protein Tuberous Sclerosis Complex 2 Protein Tumor Suppressor Proteins Insulin-Like Growth Factor I Protein Kinases MTOR protein, human Ribosomal Protein S6 Kinases TOR Serine-Threonine Kinases Monomeric GTP-Binding Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Huang Jingxiang
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Manning Brendan D
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
1470-8728
DOI
10.1042/BJ20080281
Published
2008-06-01
Pages
179-90
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC2735030
Subset
IM
Grants
NCI NIH HHS · P01 CA120964 · United States
NCI NIH HHS · R01 CA122617-02 · United States
NCI NIH HHS · R01 CA122617 · United States
NCI NIH HHS · P01-CA120964 · United States
NCI NIH HHS · P01 CA120964-02 · United States
NCI NIH HHS · R01-CA122617 · United States
External Links
PubMed source DOI: 10.1042/BJ20080281 PMC Full Text View journal details
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