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.
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DOI：
10.1111/pcmr.12721
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发表时间：
2019-01
影响因子：
4.3
通讯作者：
Steingrimsson E
中科院分区：
文献类型：
--
作者：
Fock V;Gudmundsson SR;Gunnlaugsson HO;Stefansson JA;Ionasz V;Schepsky A;Viarigi J;Reynisson IE;Pogenberg V;Wilmanns M;Ogmundsdottir MH;Steingrimsson E
小眼症相关转录因子（MITF）是碱性螺旋-环-螺旋亮氨酸拉链（bHLH-Zip）家族的成员，并且作为黑素细胞谱系的主调节因子起作用。MITF-M是在黑素细胞和黑素瘤细胞中表达的主要亚型，并且与其他MITF亚型不同，它是组成性核的。突变分析揭示了MITF-M的bHLH-Zip结构域中的三个嗜核信号，跨越残基197-206、214-217和255-265。MITF蛋白的结构表征表明，这些信号中的碱性残基在没有DNA的情况下暴露于相互作用。此外，我们的数据表明，既不DNA结合，也不二聚化的MITF-M所需的核定位。最后，与野生型蛋白相比，二聚化缺陷的MITF-M突变体在黑素瘤细胞中表现出显著降低的稳定性。两者合计，我们已经表明，除了其在DNA结合和二聚体形成中的既定作用，MITF的bHLH-Zip结构域调节转录因子的亚细胞定位和稳定性。
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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影响因子：
64.8
作者：
Bertolotto, Corine;Lesueur, Fabienne;Bressac-de Paillerets, Brigitte
通讯作者：
Bressac-de Paillerets, Brigitte
影响因子：
64.8
作者：
Perera, RushikaM.;Stoykova, Svetlana;Nicolay, Brandon N.;Ross, Kenneth N.;Fitamant, Julien;Boukhali, Myriam;Lengrand, Justine;Deshpande, Vikram;Selig, Martin K.;Ferrone, Cristina R.;Settleman, Jeff;Stephanopoulos, Gregory;Dyson, Nicholas J.;Zoncu, Roberto;Ramaswamy, Sridhar;Haas, Wilhelm;Bardeesy, Nabeel
通讯作者：
Bardeesy, Nabeel
影响因子：
21.3
作者：
Medina DL;Di Paola S;Peluso I;Armani A;De Stefani D;Venditti R;Montefusco S;Scotto-Rosato A;Prezioso C;Forrester A;Settembre C;Wang W;Gao Q;Xu H;Sandri M;Rizzuto R;De Matteis MA;Ballabio A
通讯作者：
Ballabio A
影响因子：
4.3
作者：
Cronin JC;Wunderlich J;Loftus SK;Prickett TD;Wei X;Ridd K;Vemula S;Burrell AS;Agrawal NS;Lin JC;Banister CE;Buckhaults P;Rosenberg SA;Bastian BC;Pavan WJ;Samuels Y
通讯作者：
Samuels Y
影响因子：
3.5
作者：
Grill, Christine;Bergsteinsdottir, Kristin;Steingrimsson, Eirikur
通讯作者：
Steingrimsson, Eirikur