We have located links that may give you full text access.
Journal Article
Review
Evidence to suggest that expression of MITF induces melanocyte differentiation and haploinsufficiency of MITF causes Waardenburg syndrome type 2A.
Pigment Cell Research 1997 Februrary
MITF (microphthalmia-associated transcription factor) encodes a transcription factor with a basic-helix-loop-helix-leucine zipper (bHLH-Zip) motif. Ectopic expression of MITF is found to convert NIH/3T3 fibroblasts into cells with characteristics of melanocytes. MITF transfectants formed foci, which superficially resembled those induced by oncogenes, but did not exhibit malignant phenotypes. Instead, they contained dendritic cells that express melanogenic marker proteins such as tyrosinase and tyrosinase-related protein 1. Such properties were not observed in cells transfected with the closely related gene, TFE3. These findings indicated that MITF is involved in melanocyte differentiation. Two mutations (C760-->T and C895-->T) in MITF are found to be associated with individuals with Waardenburg syndrome type 2 (WS2). These mutations create stop codons in exon 7 and 8, respectively, and probably result in truncated proteins lacking HLH-Zip or Zip structure. To understand how these MITF mutations cause WS2 in heterozygotes, mutant MITF proteins were generated and used for DNA-binding and luciferase reporter assays. The mutated MITF proteins lose their DNA-binding activity and fail to transactivate the promoter of the tyrosinase gene. However, these mutated proteins do not appear to interfere with the activity of wild-type MITF protein in these assays, indicating that they do not show a dominant-negative effect. These findings suggest that the phenotypes of the two WS2 families are caused by loss-of-function mutations in one of the two MITF alleles, resulting in haploinsufficiency of the MITF protein, the transcription factor necessary for normal melanocyte differentiation.
Full text links
Related Resources
Trending Papers
Challenges in Septic Shock: From New Hemodynamics to Blood Purification Therapies.Journal of Personalized Medicine 2024 Februrary 4
Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection.International Journal of Molecular Sciences 2024 April 4
The 'Ten Commandments' for the 2023 European Society of Cardiology guidelines for the management of endocarditis.European Heart Journal 2024 April 18
A Guide to the Use of Vasopressors and Inotropes for Patients in Shock.Journal of Intensive Care Medicine 2024 April 14
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app