Molecular Mechanisms of Notch Signaling in Neoplasia
Annual summary rept. 1 Aug 2001-31 Jul 2002
CINCINNATI UNIV OH
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The purpose of this study is to identify the molecular mechanisms by which constitutive - expression of activated Notch alleles induces neoplasia. We hypothesize that neoplastic conversion of cells by Notch proteins proceeds through nuclear protein interactions within the previously identified minimal transformation domain. This work will identify protein partners Notch proteins utilize as effectors of neoplastic signal propagation. A major finding during the past year has been the identification and characterization of a high- molecular-weight Notch complex in the nucleus of cells transformed by Notch. This complex contains both CSL and Mastermind in addition to Notch and our data indicates that formation of this complex is likely required for neoplastic transformation by Notch. Current research is focused upon the function of Mastermind in both complex formation and activity in addition to characterization of complex formation by other Notch family members. Funding for this proposal over the past year has resulted in the publication of - one manuscript, and the presentation of one poster and one oral presentation at scientific meetings.
- Medicine and Medical Research