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User guide to MiT-TFE isoforms and post-translational modifications
Hong Nhung Vu1, Ramile Dilshat1, Valerie Fock1
1Department of Biochemistry and Molecular Biology, BioMedical Center, Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
Abstract:
The microphthalmia-associated transcription factor (MITF) is at the core of melanocyte and melanoma fate specification. The related factors TFEB and TFE3 have been shown to be instrumental for transcriptional regulation of genes involved in lysosome biogenesis and autophagy, cellular processes important for mediating nutrition signals and recycling of cellular materials, in many cell types. The MITF, TFEB, TFE3, and TFEC proteins are highly related. They share many structural and functional features and are targeted by the same signaling pathways. However, the existence of several isoforms of each factor and the increasing number of residues shown to be post-translationally modified by various signaling pathways poses a difficulty in indexing amino acid residues in different isoforms across the different proteins. Here, we provide a resource manual to cross-reference amino acids and post-translational modifications in all isoforms of the MiT-TFE family in humans, mice, and zebrafish and summarize the protein accession numbers for each isoform of these factors in the different genomic databases. This will facilitate future studies on the signaling pathways that regulate different isoforms of the MiT-TFE transcription factor family.
Insights
This study provides a manual for cross-referencing amino acids and post-translational modifications in the MiT-TFE transcription factor family. This resource aids research into signaling pathways regulating these key factors in cell fate.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- The microphthalmia-associated transcription factor (MITF) family, including TFEB and TFE3, regulates melanocyte and melanoma cell fate.
- These factors are crucial for lysosome biogenesis and autophagy, essential cellular recycling processes.
- Challenges exist in standardizing the indexing of amino acid residues and post-translational modifications across different isoforms and related proteins.
Purpose of the Study:
- To create a comprehensive resource for cross-referencing amino acids and post-translational modifications within the MiT-TFE transcription factor family.
- To facilitate standardized research on the signaling pathways affecting MiT-TFE isoforms.
- To provide protein accession numbers for all isoforms in major genomic databases.
Main Methods:
- Compilation of data on MITF, TFEB, TFE3, and TFEC isoforms across humans, mice, and zebrafish.
- Cross-referencing of amino acid residues and known post-translational modifications.
- Summarization of protein accession numbers from genomic databases.
Main Results:
- A detailed manual is presented for the MiT-TFE family, covering all isoforms in humans, mice, and zebrafish.
- The manual includes cross-referenced amino acid positions and post-translational modification sites.
- Protein accession numbers for each isoform are cataloged.
Conclusions:
- This resource simplifies the study of signaling pathways impacting MiT-TFE family members.
- Standardized indexing of post-translational modifications will enhance comparative and functional analyses.
- Facilitates future research into cell fate determination and cellular recycling mechanisms regulated by MiT-TFE factors.
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