Characterization of the Nucleolar Gene Product, Treacle, in Treacher Collins Syndrome
AUTOR(ES)
Isaac, Cynthia
FONTE
The American Society for Cell Biology
RESUMO
Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development caused by mutations in the gene TCOF1. Its gene product, treacle, consists mainly of a central repeat domain, which shows it to be structurally related to the nucleolar phosphoprotein Nopp140. Treacle remains mostly uncharacterized to date. Herein we show that it, like Nopp140, is a highly phosphorylated nucleolar protein. However, treacle fails to colocalize with Nopp140 to Cajal (coiled) bodies. As in the case of Nopp140, casein kinase 2 appears to be responsible for the unusually high degree of phosphorylation as evidenced by its coimmunoprecipitation with treacle. Based on these and other observations, treacle and Nopp140 exhibit distinct but overlapping functions. The majority of TCOF1 mutations in TCS lead to premature termination codons that could affect the cellular levels of the full-length treacle. We demonstrate however, that the cellular amount of treacle varies less than twofold among a collection of primary fibroblasts and lymphoblasts and regardless of whether the cells were derived from TCS patients or healthy individuals. Therefore, cells of TCS patients possess a mechanism to maintain wild-type levels of full-length treacle from a single allele.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=14975Documentos Relacionados
- Treacher Collins syndrome.
- TCOF1 gene encodes a putative nucleolar phosphoprotein that exhibits mutations in Treacher Collins Syndrome throughout its coding region
- The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor
- Molecular analysis of the TCOF1 gene in Treacher Collins syndrome patients
- Ophthalmic features and visual prognosis in the Treacher-Collins syndrome.