Molecular Mechanisms of Glial Abnormalitites in Neurofibromatosis
Abstract
Schwann cells proliferation appears to be controlled by cAMP, implicating CREB, and the CREB-binding protein. CBP specifically modulate cAMP and ras-dependent growth events in glia. This is likely to underlie the misregulation in Schwann cell proliferation associated with neurofibromatosis type 1, in which two copies of the NF1 gene are functionally in active. The characterization of CBP as an integrator of cAMP and ras-related growth factor responses, together with the observation that limiting CBP can result in AP-1 inhibiting events, has led us to explore the role of CBP, transcriptional coactivators, and associated transcription factors in these events. Representational difference analysis has been modified to deterrnine the gene traits responsible for ordered and abnormal transcriptional responses in genetic models designed to alter cAMP- and ras-dependent signaling pathways, permitting identification and characterization of factors which contribute to the etiology of neurofibromatosis type 1. We have succeeded in perfecting a method that identified bona fide targets, as experimentally demonstrated. We have investigated the cooperative nature of regulatory interfaces between transcriptional coactivators and transcription factors, and find that specific interactions of transcriptional coactivators with CBP act to dictate the choice between transcriptional activation and quiescence under conditions of elevated second messenger signaling mechanisms.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA389570
Entities
People
- Michael G. Rosenfeld
Organizations
- University of California, San Diego