The role of tuberin in cellular differentiation: are B-Raf and MAPK involved?
Ann N Y Acad Sci
; 1059: 168-73, 2005 Nov.
Article
em En
| MEDLINE
| ID: mdl-16382052
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.
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Bases de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
/
Sistema de Sinalização das MAP Quinases
/
Proteínas Supressoras de Tumor
/
Proteínas Proto-Oncogênicas B-raf
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Ann N Y Acad Sci
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos