The Role of Tuberin in Cellular Differentiation: Are B-Raf and MAPK Involved?
Article first published online: 9 JAN 2006
Annals of the New York Academy of Sciences
Volume 1059, Tumor Progression and Therapeutic Resistance pages 168–173, November 2005
How to Cite
KARBOWNICZEK, M. and HENSKE, E. P. (2005), The Role of Tuberin in Cellular Differentiation: Are B-Raf and MAPK Involved?. Annals of the New York Academy of Sciences, 1059: 168–173. doi: 10.1196/annals.1339.045
- Issue published online: 9 JAN 2006
- Article first published online: 9 JAN 2006
- tuberous sclerosis complex;
Abstract: Tuberous sclerosis complex (TSC) is a tumor suppressor gene syndrome whose manifestations can include seizures, mental retardation, autism, and tumors in the brain, retina, kidney, heart, and skin. The products of the TSC1 and TSC2 genes, hamartin and tuberin, respectively, heterodimerize and inhibit the mammalian target of rapamycin (mTOR). This review focuses on the genetic and biochemical basis of the renal and pulmonary manifestations of TSC, angiomyolipomas, and lymphangiomyomatosis, respectively. Genetic analyses of sporadic angiomyolipomas revealed that all three components (smooth muscle, vessels, and fat) derive from a common progenitor cell, indicating the ability of cells lacking tuberin to differentiate into multiple lineages. Other genetic studies showed that the benign smooth muscle cells of pulmonary lymphangiomyomatosis have the ability to migrate to other organs. These findings suggest that tuberin and hamartin play a role in the regulation of cellular migration and differentiation. We have found that tuberin activates B-Raf kinase and p42/44 MAPK and that cells lacking tuberin have low levels of B-Raf activity. We hypothesize that aberrant B-Raf activity in angiomyolipomas leads to abnormal cellular differentiation and migration.