Subcellular localization and stability of MITF are modulated by the bHLH‐Zip domain

Subcellular localization and stability of MITF are modulated by the bHLH‐Zip domain

Summary 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...

Full description

Saved in:
Bibliographic Details
Published in:Pigment cell and melanoma research Vol. 32; no. 1; pp. 41 - 54
Main Authors: Fock, Valerie, Gudmundsson, Sigurdur Runar, Gunnlaugsson, Hilmar Orn, Stefansson, Jon August, Ionasz, Vivien, Schepsky, Alexander, Viarigi, Jade, Reynisson, Indridi Einar, Pogenberg, Vivian, Wilmanns, Matthias, Ogmundsdottir, Margret Helga, Steingrimsson, Eirikur
Format: Journal Article
Language:English
Published: England Wiley Subscription Services, Inc 01-01-2019
Subjects:
bHLH‐Zip
Binding
Deoxyribonucleic acid
Dimerization
Dimers
DNA
Helix-loop-helix proteins (basic)
Isoforms
Leucine
Leucine zipper proteins
Localization
Melanocytes
Melanoma
Microphthalmia-associated transcription factor
MITF
Mutants
nuclear localization
Proteins
Residues
Stability
Structural analysis
Transcription factors
Waardenburg syndrome
nuclear localization
MITF
Waardenburg syndrome
bHLH-Zip
stability
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary 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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1755-1471
1755-148X
DOI:10.1111/pcmr.12721