Tudor tells about new twists in the story tale of SMURFs.

Smad ubiquitin regulatory factors (SMURFS) belong to the HECT- family of E3 ubiquitin ligases. This family has two members, SMURF1 and SMURF2. SMURFs have emerged as well studied negative regulators of TGF induced intracellular signaling. However, increasingly it is being realized that SMURFs tactfully modulate an array of proteins in different cancers. This review sets spotlight on how SMURF1 and SMURF2 communicate with effectors of different signaling pathways during the multistep progression to cancer. We also summarize how microRNAs (miRNAs) effectively control SMURFs in different cancers. Role of SMURFs is context dependent in different cancers and better concepts related to miRNA regulation of SMURFs in different stages and steps of cancer will be helpful in efficient translation of laboratory findings to clinic.

Two novel mutations in the gene EDAR causing autosomal recessive hypohidrotic ectodermal dysplasia.

INTRODUCTION: Hypohidrotic ectodermal dysplasia (HED) is a human heritable disorder characterized by sparse hair, reduced ability to sweat and hypodontia. The HED exhibits X-linked, autosomal recessive and autosomal dominant mode of inheritance. Mutations in four genes including EDA, EDAR, EDARADD, and WNT10A are known to cause hypohidrotic and anhidrotic ectodermal dysplasia. MATERIALS AND METHODS: Genotyping of both affected and normal individuals of two consanguineous Pakistani families (A, B), showing autosomal recessive HED, was carried out using microsatellite markers linked to EDAR gene on chromosome 2q11-q13. To screen for mutations in the gene EDAR, all of its exons and splice junction were amplified and sequenced directly, using an automated DNA sequencer. RESULTS: Genotyping using microsatellite markers analysis showed linkage of the two families to gene EDAR on chromosome 2q11-2q13. Subsequently, screening of all the 12 exons and splice junctions of gene EDAR revealed a novel missense mutation (c.1163T>C; p.Ile388Thr) in family A and a novel insertion mutation (c.1014insA; p.V339SfsX6) in family B. CONCLUSION: Our findings extend the body of evidence supporting the role of EDAR signaling pathway as a powerful regulator of development of ectodermal appendages.