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

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Subcellular localization and stability of MITF are modulated by the bHLH-Zip domain. / 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.

In: PIGM CELL MELANOMA R, Vol. 32, No. 1, 01.2019, p. 41-54.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Fock, V, Gudmundsson, SR, Gunnlaugsson, HO, Stefansson, JA, Ionasz, V, Schepsky, A, Viarigi, J, Reynisson, IE, Pogenberg, V, Wilmanns, M, Ogmundsdottir, MH & Steingrimsson, E 2019, 'Subcellular localization and stability of MITF are modulated by the bHLH-Zip domain', PIGM CELL MELANOMA R, vol. 32, no. 1, pp. 41-54. https://doi.org/10.1111/pcmr.12721

APA

Fock, V., Gudmundsson, S. R., Gunnlaugsson, H. O., Stefansson, J. A., Ionasz, V., Schepsky, A., Viarigi, J., Reynisson, I. E., Pogenberg, V., Wilmanns, M., Ogmundsdottir, M. H., & Steingrimsson, E. (2019). Subcellular localization and stability of MITF are modulated by the bHLH-Zip domain. PIGM CELL MELANOMA R, 32(1), 41-54. https://doi.org/10.1111/pcmr.12721

Vancouver

Fock V, Gudmundsson SR, Gunnlaugsson HO, Stefansson JA, Ionasz V, Schepsky A et al. Subcellular localization and stability of MITF are modulated by the bHLH-Zip domain. PIGM CELL MELANOMA R. 2019 Jan;32(1):41-54. https://doi.org/10.1111/pcmr.12721

Bibtex

@article{7b0ce59532614e268d73a50407580f73,
title = "Subcellular localization and stability of MITF are modulated by the bHLH-Zip domain",
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.",
keywords = "Amino Acid Sequence, Arginine/metabolism, Cell Line, Cell Nucleus/metabolism, Helix-Loop-Helix Motifs, Humans, Microphthalmia-Associated Transcription Factor/chemistry, Protein Domains, Protein Multimerization, Protein Stability, Protein Transport, Subcellular Fractions/metabolism",
author = "Valerie Fock and Gudmundsson, {Sigurdur Runar} and Gunnlaugsson, {Hilmar Orn} and Stefansson, {Jon August} and Vivien Ionasz and Alexander Schepsky and Jade Viarigi and Reynisson, {Indridi Einar} and Vivian Pogenberg and Matthias Wilmanns and Ogmundsdottir, {Margret Helga} and Eirikur Steingrimsson",
note = "{\textcopyright} 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",
year = "2019",
month = jan,
doi = "10.1111/pcmr.12721",
language = "English",
volume = "32",
pages = "41--54",
journal = "PIGM CELL MELANOMA R",
issn = "1755-1471",
publisher = "Wiley-Blackwell",
number = "1",

}

RIS

TY - JOUR

T1 - Subcellular localization and stability of MITF are modulated by the bHLH-Zip domain

AU - Fock, Valerie

AU - Gudmundsson, Sigurdur Runar

AU - Gunnlaugsson, Hilmar Orn

AU - Stefansson, Jon August

AU - Ionasz, Vivien

AU - Schepsky, Alexander

AU - Viarigi, Jade

AU - Reynisson, Indridi Einar

AU - Pogenberg, Vivian

AU - Wilmanns, Matthias

AU - Ogmundsdottir, Margret Helga

AU - Steingrimsson, Eirikur

N1 - © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2019/1

Y1 - 2019/1

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - Arginine/metabolism

KW - Cell Line

KW - Cell Nucleus/metabolism

KW - Helix-Loop-Helix Motifs

KW - Humans

KW - Microphthalmia-Associated Transcription Factor/chemistry

KW - Protein Domains

KW - Protein Multimerization

KW - Protein Stability

KW - Protein Transport

KW - Subcellular Fractions/metabolism

U2 - 10.1111/pcmr.12721

DO - 10.1111/pcmr.12721

M3 - SCORING: Journal article

C2 - 29938923

VL - 32

SP - 41

EP - 54

JO - PIGM CELL MELANOMA R

JF - PIGM CELL MELANOMA R

SN - 1755-1471

IS - 1

ER -