Abstract
The LKB1 tumor suppressor protein controls the activity of the TSC1/TSC2 tumor suppressor complex. Mutations in LKB1 cause Peutz-Jeghers syndrome (PJS), and mutations in either TSC1 or TSC2 cause tuberous sclerosis complex--two syndromes characterized by the development of hamartomas. LKB1 activation by energy deprivation activates AMPK, which in turn phosphorylates and activates TSC2. TSC2 activation results in the inactivation of mTOR, a critical regulator of protein translation. How mTOR dysregulation after inactivation of LKB1 or TSC1/2 contributes to hamartoma development is not known. However, hypoxia-inducible factor (HIF) and VEGF are regulated by mTOR and are likely to play a contributory role.
MeSH terms
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AMP-Activated Protein Kinase Kinases
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Animals
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DNA-Binding Proteins / metabolism*
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Hamartoma / genetics
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Hamartoma / metabolism*
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Humans
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Hypoxia-Inducible Factor 1
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Hypoxia-Inducible Factor 1, alpha Subunit
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Nuclear Proteins / metabolism*
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Peutz-Jeghers Syndrome / genetics
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Peutz-Jeghers Syndrome / metabolism*
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Protein Kinases / metabolism
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Protein Serine-Threonine Kinases / metabolism
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Signal Transduction
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TOR Serine-Threonine Kinases
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Transcription Factors*
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Tuberous Sclerosis / genetics
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Tuberous Sclerosis / metabolism*
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Vascular Endothelial Growth Factor A / metabolism*
Substances
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DNA-Binding Proteins
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HIF1A protein, human
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Hypoxia-Inducible Factor 1
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Hypoxia-Inducible Factor 1, alpha Subunit
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Nuclear Proteins
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Transcription Factors
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Vascular Endothelial Growth Factor A
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Protein Kinases
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MTOR protein, human
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Protein Serine-Threonine Kinases
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STK11 protein, human
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TOR Serine-Threonine Kinases
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AMP-Activated Protein Kinase Kinases