Rough growths on fingernail
Symptoms
- White patches on skin due to decrease in pigment
- Red patches on facial area
- Raised patches with orange peel texture on back
Cellular Pathway of TSC
- Developmental delays
- Intellectual disability
- Seizures
- TSC1/TSC2 receives inputs from at least three major signaling pathways in the form of kinase-mediated phosphorylation events that regulate its function as a GTPase activating protein (GAP): the PI3K-Akt pathway, the ERK1/2-RSK1 pathway and the LKB1-AMPK pathway.
- Pitted tooth enamel
- Rough growths under and around nails
- Rubbery noncancerous tumors on or around tongue
*Symptoms may vary from person to person...
GAP
vs.
Incorrect Pathway
Correct Pathway
- TSC 1 & TSC 2 acts as GAP towards
Rheb, which is the regulator of mTOR.
With Tuberin and Hamartin forming to
create the TSC tumor suppressor,
no tumors, or hamartomas, occur.
- In absence of TSC 1 of TSC 2, high levels of Rheb-GTP lead to activation of mTOR. This then leads to enhanced and deregulated synthesis of proteins and cell growth, resulting in tumors.
Tuberous Sclerosis
Current Direction of Research
The National Institute of Neurological Disorders and Stroke (NINDS) ...
- conducts TSC research in their labs at the National Institutes of Health (NIH)
- lend grants to other medical institutions to conduct their own research.
Others scientists...
- study to learn more about the genes that can cause TSC and the function of the proteins those genes produce.
- study focusing on the two major brain disorders (autism and epilepsy) that occur in children with TSC.
- try to determine what causes skin tumors to develop in individuals with TSC and to find the molecular basis of these tumors.
Where the mutations occur
How?
- A pathological mutation affects the TSC 1 and TSC 2, which are tumor-suppressor genes.
- The absence of either lead to deregulation of protein synthesis and cell growth.
TSC 1
TSC 2
- Chromosome 2, position 13.3
- Tuberin, protein created by TSC 2
- Chromosome 9, position 34
- Hamartin, protein created by TSC1
What is Tuberous Sclerosis?
According to the National Library of Medicine...
- Tuberous sclerosis is a group of two genetic disorders that affect the skin, brain/nervous system, kidneys, and heart, and cause tumors to grow. The diseases are named after a tuber- or root-shaped growth in the brain.
Basically...
- An inherited genetic disorder which occurs when a mutation happens in the TSC1 and the TSC2 genes.
Jennifer Baltazar
Kelsey Barr
AP Biology II
P.6
Work Cited
Bernards, Andre, and Jeffrey Settleman. "GAP: Regulating the Regulators of Small GTPases." GAP: Regulating the Regulators of Small GTPases. MGH Cancer Center and Harvard Medical School, 1 July 2004. Web. 30 Nov. 2013. <http://www.cell.com/trends/cell-biology/abstract/S0962-8924(04)00135-7>.
"Human Molecular Genetics." Tuberous Sclerosis: A GAP at the Crossroads of Multiple Signaling Pathways. Oxford University Press, n.d. Web. 30 Nov. 2013. <http://hmg.oxfordjournals.org/content/14/suppl_2/R251/F2.EXPANSION.HTML>.
Kwiatkowski, DJ, and Manning, BD. "Tuberous Sclerosis: A GAP at the Crossroads of Multiple Signaling Pathways." National Center for Biotechnology Information. U.S. National Library of Medicine, 15 Oct. 2005. Web. 30 Nov. 2013. <http://www.ncbi.nlm.nih.gov/pubmed/16244323>.
"Research Plan For Tuberous Sclerosis." <i>: National Institute of Neurological Disorders and Stroke (NINDS)</i>. N.p., n.d. Web. 4 Dec. 2013. <http://www.ninds.nih.gov/about_ninds/plans/tscler_research_plan.htm>.
Tee, AR, Manning, BD, Roux, PP, Cantley, LC, and Blenis, J. "Tuberous Sclerosis Complex Gene Products, Tuberin and Hamartin, Control MTOR Signaling by Acting as a GTPase-activating Protein Complex toward Rheb." US National Library of Medicine. Department of Cell Biology, Harvard Medical School, Boston, MA, 5 Aug. 2003. Web. 30 Nov. 2013. <http://www.ncbi.nlm.nih.gov/pubmed/12906785>.
"Tuberous Sclerosis(Bourneville Disease, Epiloia)." Genetics 4 Medics . N.p., 12 Feb. 2012. Web. 30 Nov. 2013. <http://genetics4medics.com/tuberous-sclerosis.html>.