AI Article Synopsis
- MITF is a key regulator in melanocytes and melanoma, with the MITF-M isoform being consistently found in the nucleus.
- Mutational analysis identified specific signals within its structure that enable nuclear localization independent of DNA binding and dimerization.
- Furthermore, dimerization-deficient mutants of MITF-M are less stable in melanoma cells, highlighting the importance of the bHLH-Zip domain in both localization and stability of the protein.
Article Abstract
Microphthalmia-associated transcription factor (MITF) is a member of the basic helix-loop-helix leucine zipper (bHLH-Zip) family and functions as the master regulator of the melanocytic lineage. MITF-M is the predominant isoform expressed in melanocytes and melanoma cells, and, unlike other MITF isoforms, it is constitutively nuclear. Mutational analysis revealed three karyophilic signals in the bHLH-Zip domain of MITF-M, spanning residues 197-206, 214-217, and 255-265. Structural characterization of the MITF protein showed that basic residues within these signals are exposed for interactions in the absence of DNA. Moreover, our data indicate that neither DNA binding nor dimerization of MITF-M are required for its nuclear localization. Finally, dimerization-deficient MITF-M mutants exhibited a significantly reduced stability in melanoma cells when compared to the wild-type protein. Taken together, we have shown that, in addition to its well-established role in DNA binding and dimer formation, the bHLH-Zip domain of MITF modulates the transcription factor's subcellular localization and stability.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611459 | PMC |
| http://dx.doi.org/10.1111/pcmr.12721 | DOI Listing |
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Article Synopsis
- MITF is a key regulator in melanocytes and melanoma, with the MITF-M isoform being consistently found in the nucleus.
- Mutational analysis identified specific signals within its structure that enable nuclear localization independent of DNA binding and dimerization.
- Furthermore, dimerization-deficient mutants of MITF-M are less stable in melanoma cells, highlighting the importance of the bHLH-Zip domain in both localization and stability of the protein.
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