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NF2/Merlin and Neurofibromatosis. Maciej S. Tobola Biol 169 Cancer Biology March 30, 2004. Type II Neurofibromatosis. Autosomal dominant Nervous System Rare Two-Hit. Merlin in Adherens Junctions. No Adherens=No Contact Inhibition. McClatchey et al., 2003. Various KO’s. NF2 -/- Mouse - PowerPoint PPT Presentation
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NF2/Merlin and NF2/Merlin and NeurofibromatosisNeurofibromatosis
Maciej S. TobolaMaciej S. TobolaBiol 169 Cancer BiologyBiol 169 Cancer Biology
March 30, 2004March 30, 2004
Type II NeurofibromatosisType II Neurofibromatosis
Autosomal dominantAutosomal dominant Nervous SystemNervous System RareRare Two-HitTwo-Hit
Merlin in Adherens JunctionsMerlin in Adherens Junctions
No Adherens=No Contact InhibitionNo Adherens=No Contact Inhibition
McClatchey et al., 2003
Various KO’sVarious KO’s
NF2NF2-/--/- Mouse Mouse• Dies QuicklyDies Quickly
Conditional NF2Conditional NF2-/--/- Mouse Mouse• Many SchwannomasMany Schwannomas
Drosophila Bluebox MutantDrosophila Bluebox Mutant• Overproliferation in wingOverproliferation in wing
NF2NF2
Chromosome 22Chromosome 22
Nonsense & Frameshift mutationsNonsense & Frameshift mutations DeletionsDeletions
http://www.rzpd.de/cgi-bin/cards/carddisp?NF2
MerlinMerlin
Protein 4.1 SuperfamilyProtein 4.1 Superfamily
Gutmann et al., 2002
Merlin StructureMerlin Structure
Blue BoxBlue Box A-C Salt BridgeA-C Salt Bridge
Gutmann et al., 2002
Activity in the CellActivity in the Cell
Open=InactiveOpen=Inactive Closed=Active Tumor SuppressorClosed=Active Tumor Suppressor
OpenClosed
Gutmann et al., 2002
Activity in the CellActivity in the Cell
McClatchey et al., 2003
NeurofibromatosisNeurofibromatosis
No Rac1 InhibitionNo Rac1 InhibitionMerlin PhoshorylationMerlin PhoshorylationIncreased ProliferationIncreased Proliferation
McClatchey et al., 2003
Remember This?Remember This?
No Adherens=No Contact InhibitionNo Adherens=No Contact Inhibition
McClatchey et al., 2003
Cancer RecipeCancer Recipe
Increased Proliferation +Increased Proliferation +
Loss of Contact Inhibition =Loss of Contact Inhibition =
Neurofibromatosis Type II
http://www.neurofibromatosis.org/what_is_nf/nf2_technical.htm
Treatment OptionsTreatment Options
SurgerySurgery• Location complicationsLocation complications
Focused Radiation TherapyFocused Radiation Therapy
Sign LanguageSign Language