Hamartin and tuberin: Working together for tumour suppression

TSC1 and TSC2 are two recently identified tumour suppressor genes encoding hamartin and tuberin, respectively, and involved in pathogenesis of tuberous sclerosis, neurological disorder connected with the development of hamartomas in numerous organ systems, including the brain, kidneys, heart and liv...

Full description

Saved in:
Bibliographic Details
Published in:International journal of cancer 2006-01, Vol.118 (1), p.1-5
Main Author: Jozwiak, Jaroslaw
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Cell Transformation, Neoplastic
Fundamental and applied biological sciences. Psychology
Growth Substances - biosynthesis
hamartin
Hamartoma - physiopathology
Humans
Medical sciences
Molecular and cellular biology
Monomeric GTP-Binding Proteins - metabolism
mTOR
Neuropeptides - metabolism
Phosphorylation
Phosphotransferases - metabolism
Ras Homolog Enriched in Brain Protein
tuberin
Tumor Suppressor Proteins - metabolism
Tumor Suppressor Proteins - physiology
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:TSC1 and TSC2 are two recently identified tumour suppressor genes encoding hamartin and tuberin, respectively, and involved in pathogenesis of tuberous sclerosis, neurological disorder connected with the development of hamartomas in numerous organ systems, including the brain, kidneys, heart and liver. Both protein products of TSC1 and TSC2 form an intracellular complex exerting GTPase‐activating (GAP) activity towards a small G protein, Ras homologue enriched in brain (Rheb). Inhibition of Rheb is important for the regulation of mTOR pathway, while mutation of hamartin or tuberin results in uncontrolled cell cycle progression. Tuberin, possessing the Rheb‐GAP domain, is phosphorylated by several kinases that confer the signals of growth factor stimulation or low cellular energy levels. Such a modification of tuberin influences its activity within the complex with hamartin and positively or negatively modulates mTOR‐regulated protein translation and cellular proliferation. Current article describes biochemical properties of hamartin and tuberin, their known regulatory phosphorylation sites and binding partners. © 2005 Wiley‐Liss, Inc.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.21542