Abstract
BackgroundWTX is a novel gene mutated in a proportion of Wilms' tumors and in patients suffering from sclerosing bone dysplasia. On the molecular level WTX has been shown to act as an antagonist of canonical Wnt/β-catenin signaling in fish and mammals thus linking it to an essential pathway involved in normal development and cancer formation. Interestingly, WTX seems to also localize to an intranuclear component called paraspeckles. In spite of the growing interest of molecular biologists in WTX, little is known about its paralogs and its phylogenetic history.ResultsUsing the amino-acid sequence of WTX/AMER1 as a tool for the assignment of orthology and paralogy, we here identify two novel proteins, AMER2 and AMER3, as "WTX" related. This Amer gene family is present in all currently available vertebrate genome sequences, but not invertebrate genomes and is characterized by six conserved blocks of sequences. The phylogenetic analysis suggests that the protoAmer gene originated early in the vertebrate lineage and was then duplicated due to whole genome duplications (WGD) giving rise to the three different Amer genes.ConclusionOur study represents the first phylogenetic analysis of Amer genes and reveals a new vertebrate specific gene family that is likely to have played an important role in the evolution of this subphylum. Divergent and conserved molecular functions of Wtx/Amer1, Amer2 and Amer3 are discussed.
Highlights
WTX is a novel gene mutated in a proportion of Wilms’ tumors and in patients suffering from sclerosing bone dysplasia
Wtx/Amer1 physically interacts with adenomatous polyposis coli (APC) [3], a tumor suppressor gene involved in colorectal cancer [4]
The mouse and human APC membrane recruitment (AMER) proteins are encoded by a single exon 5’ untranslated sequences map to additional exons
Summary
WTX is a novel gene mutated in a proportion of Wilms’ tumors and in patients suffering from sclerosing bone dysplasia. On the molecular level WTX has been shown to act as an antagonist of canonical Wnt/bcatenin signaling in fish and mammals linking it to an essential pathway involved in normal development and cancer formation. Using large-scale interactome mapping a second independent study demonstrated that WTX induces degradation of b-catenin via the proteasome system, identifying this gene as an important modulator of this crucial signaling pathway [2]. Recent analysis suggests that WTX may play an important function during normal development: expression analysis demonstrated a dynamic expression pattern throughout embryogenesis [6] and mutations have been identified in patients suffering from a range of developmental defects including osteopathia striata congenita with cranial
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