Novel Molecular Interactions and Biological Functions of the Neurofibromatosis 2 Tumor Suppressor Protein, Merlin
Annual rept. 29 Jul 2005-28 Jul 2006
HELSINKI UNIV (FINLAND)
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The project studies molecular functions of neurofibromatosis 2 tumor suppressor protein merlin and compares the role of phosphorylation in regulation of merlin and structurally related ezrin. The role of different importin subunits in nuclear targeting of merlin was tested. Merlin bound several importin subunits in a non-selective manner. Merlin was shown to bind tubulin via two different rngions one located in the FERM-domain and one at the C-terminus. Intramolecular association and phosphorylation of S518 residue regulated tubulin binding. Merlin promoted microtubule polymerization in vitro and in vivo. Loss of merlin caused marked changes in microtubule organization and dynamics. Studies on merlin and HEI10 a cell cycle rngulator clarified the interaction mechanism and showed a role for merlin in regulation of the integrity of HEI10. Phosphorylation studies identified a second protein kinase A binding site in merlin. Finally studies assessing the role of Src-induced tyrosine phosphorylation of ezrin were initiated.