MITF drives endolysosomal biogenesis and potentiates Wnt signaling in melanoma cells.

Abstract:

:Canonical Wnt signaling plays an important role in development and disease, regulating transcription of target genes and stabilizing many proteins phosphorylated by glycogen synthase kinase 3 (GSK3). We observed that the MiT family of transcription factors, which includes the melanoma oncogene MITF (micropthalmia-associated transcription factor) and the lysosomal master regulator TFEB, had the highest phylogenetic conservation of three consecutive putative GSK3 phosphorylation sites in animal proteomes. This finding prompted us to examine the relationship between MITF, endolysosomal biogenesis, and Wnt signaling. Here we report that MITF expression levels correlated with the expression of a large subset of lysosomal genes in melanoma cell lines. MITF expression in the tetracycline-inducible C32 melanoma model caused a marked increase in vesicular structures, and increased expression of late endosomal proteins, such as Rab7, LAMP1, and CD63. These late endosomes were not functional lysosomes as they were less active in proteolysis, yet were able to concentrate Axin1, phospho-LRP6, phospho-β-catenin, and GSK3 in the presence of Wnt ligands. This relocalization significantly enhanced Wnt signaling by increasing the number of multivesicular bodies into which the Wnt signalosome/destruction complex becomes localized upon Wnt signaling. We also show that the MITF protein was stabilized by Wnt signaling, through the novel C-terminal GSK3 phosphorylations identified here. MITF stabilization caused an increase in multivesicular body biosynthesis, which in turn increased Wnt signaling, generating a positive-feedback loop that may function during the proliferative stages of melanoma. The results underscore the importance of misregulated endolysosomal biogenesis in Wnt signaling and cancer.

authors

Ploper D,Taelman VF,Robert L,Perez BS,Titz B,Chen HW,Graeber TG,von Euw E,Ribas A,De Robertis EM

doi

10.1073/pnas.1424576112

subject

Has Abstract

pub_date

2015-02-03 00:00:00

pages

E420-9

issue

5

eissn

0027-8424

issn

1091-6490

pii

1424576112

journal_volume

112

pub_type

杂志文章
  • Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer's disease.

    abstract::Substantial evidence from epidemiological, pathological, and clinical reports suggests that vascular factors are critical in the pathogenesis of Alzheimer's disease (AD), and changes in blood flow are currently the most reliable indicators of the disease. We previously reported that older APP23 transgenic (tg) mice ha...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0709788105

    authors: Meyer EP,Ulmann-Schuler A,Staufenbiel M,Krucker T

    更新日期:2008-03-04 00:00:00

  • Chimeric tumor necrosis factor-TrkA receptors reveal that ligand-dependent activation of the TrkA tyrosine kinase is sufficient for differentiation and survival of PC12 cells.

    abstract::To elucidate the function of the two nerve growth factor (NGF) receptors, p75NGFR and p140trk, chimeric molecules were constructed of tumor necrosis factor (TNF) and NGF receptors. Rat PC12 pheochromocytoma cells transiently transfected with TNF-p140trk chimeras, which contain the extracellular domain of TNF receptor ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.18.8717

    authors: Rovelli G,Heller RA,Canossa M,Shooter EM

    更新日期:1993-09-15 00:00:00

  • Rapid activation of protein kinase C in isolated rat liver nuclei by prolactin, a known hepatic mitogen.

    abstract::Rat liver nuclei pure by enzymatic and electron microscope criteria contain protein kinase C (PKC) that can be activated several hundredfold within 3 min of addition of prolactin or phorbol 12-tetradecanoate 13-acetate. Rat prolactin stimulated PKC maximally at 10(-12) M, whereas ovine prolactin was maximally stimulat...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.22.8649

    authors: Buckley AR,Crowe PD,Russell DH

    更新日期:1988-11-01 00:00:00

  • Voltage-gated calcium flux mediates Escherichia coli mechanosensation.

    abstract::Electrically excitable cells harness voltage-coupled calcium influx to transmit intracellular signals, typically studied in neurons and cardiomyocytes. Despite intense study in higher organisms, investigations of voltage and calcium signaling in bacteria have lagged due to their small size and a lack of sensitive tool...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1703084114

    authors: Bruni GN,Weekley RA,Dodd BJT,Kralj JM

    更新日期:2017-08-29 00:00:00

  • Parasite sequestration in Plasmodium falciparum malaria: spleen and antibody modulation of cytoadherence of infected erythrocytes.

    abstract::Sequestration, the adherence of infected erythrocytes containing late developmental stages of the parasite (trophozoites and schizonts) to the endothelium of capillaries and venules, is characteristic of Plasmodium falciparum infections. We have studied two host factors, the spleen and antibody, that influence sequest...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.16.5075

    authors: David PH,Hommel M,Miller LH,Udeinya IJ,Oligino LD

    更新日期:1983-08-01 00:00:00

  • Monoallelic silencing and haploinsufficiency in early murine intestinal neoplasms.

    abstract::Studies of tumors from human familial adenomatous polyposis, sporadic colon cancer, and mouse and rat models of intestinal cancer indicate that the majority of early adenomas develop through loss of normal function of the Adenomatous polyposis coli (APC) gene. In murine models of familial adenomatous polyposis, specif...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1120753109

    authors: Amos-Landgraf JM,Irving AA,Hartman C,Hunter A,Laube B,Chen X,Clipson L,Newton MA,Dove WF

    更新日期:2012-02-07 00:00:00

  • Designing amino acids to determine the local conformations of peptides.

    abstract::The local conformations of proteins and peptides are determined by the amino acid sequence. However, the 20 amino acids encoded by the genome allow the peptide backbone to fold into many conformations, so that even for a small peptide it becomes very difficult to predict the three-dimensional structure. By using empir...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.7.2649

    authors: Burgess AW

    更新日期:1994-03-29 00:00:00

  • Evolutionary EST analysis identifies rapidly evolving male reproductive proteins in Drosophila.

    abstract::Sequence comparisons of genomes or expressed sequence tags (ESTs) from related organisms provide insight into functional conservation and diversification. We compare the sequences of ESTs from the male accessory gland of Drosophila simulans to their orthologs in its close relative Drosophila melanogaster, and demonstr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.131568198

    authors: Swanson WJ,Clark AG,Waldrip-Dail HM,Wolfner MF,Aquadro CF

    更新日期:2001-06-19 00:00:00

  • Action video game play facilitates the development of better perceptual templates.

    abstract::The field of perceptual learning has identified changes in perceptual templates as a powerful mechanism mediating the learning of statistical regularities in our environment. By measuring threshold-vs.-contrast curves using an orientation identification task under varying levels of external noise, the perceptual templ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1417056111

    authors: Bejjanki VR,Zhang R,Li R,Pouget A,Green CS,Lu ZL,Bavelier D

    更新日期:2014-11-25 00:00:00

  • Lineage specification of neuronal precursors in the mouse spinal cord.

    abstract::We have investigated the differentiation potential of precursor cells within the developing spinal cord of mice and have shown that spinal cord cells from embryonic day 10 specifically give rise to neurons when plated onto an astrocytic monolayer, Ast-1. These neurons had the morphology of motor neurons and > 83% expr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.22.10079

    authors: Richards LJ,Murphy M,Dutton R,Kilpatrick TJ,Puche AC,Key B,Tan SS,Talman PS,Bartlett PF

    更新日期:1995-10-24 00:00:00

  • Chimpanzee super strength and human skeletal muscle evolution.

    abstract::Since at least the 1920s, it has been reported that common chimpanzees (Pan troglodytes) differ from humans in being capable of exceptional feats of "super strength," both in the wild and in captive environments. A mix of anecdotal and more controlled studies provides some support for this view; however, a critical re...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1619071114

    authors: O'Neill MC,Umberger BR,Holowka NB,Larson SG,Reiser PJ

    更新日期:2017-07-11 00:00:00

  • Massively parallel CRISPRi assays reveal concealed thermodynamic determinants of dCas12a binding.

    abstract::The versatility of CRISPR-Cas endonucleases as a tool for biomedical research has led to diverse applications in gene editing, programmable transcriptional control, and nucleic acid detection. Most CRISPR-Cas systems, however, suffer from off-target effects and unpredictable nonspecific binding that negatively impact ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1918685117

    authors: Specht DA,Xu Y,Lambert G

    更新日期:2020-05-26 00:00:00

  • Amino acid sequence of the first constant region domain and the hinge region of the delta heavy chain of human IgD.

    abstract::We have determined the amino acid sequence of the first constant (C) region domain (C delta 1) and the hinge region of the delta heavy chain of human IgD WAH and also the sequence of the adjacent COOH-terminal portion of the variable (V) region, including the JH region. Together with the sequence of the Fc fragment al...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.10.6168

    authors: Putnam FW,Takahashi N,Tetaert D,Debuire B,Lin LC

    更新日期:1981-10-01 00:00:00

  • Light-enabled reversible self-assembly and tunable optical properties of stable hairy nanoparticles.

    abstract::The ability to dynamically organize functional nanoparticles (NPs) via the use of environmental triggers (temperature, pH, light, or solvent polarity) opens up important perspectives for rapid and convenient construction of a rich variety of complex assemblies and materials with new structures and functionalities. Her...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1714748115

    authors: Chen Y,Wang Z,He Y,Yoon YJ,Jung J,Zhang G,Lin Z

    更新日期:2018-02-13 00:00:00

  • Enhanced optical properties of chemical vapor deposited single crystal diamond by low-pressure/high-temperature annealing.

    abstract::Single crystal diamond produced by chemical vapor deposition (CVD) at very high growth rates (up to 150 microm/h) has been successfully annealed without graphitization at temperatures up to 2200 degrees C and pressures <300 torr. Crystals were annealed in a hydrogen environment by using microwave plasma techniques for...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0808230105

    authors: Meng YF,Yan CS,Lai J,Krasnicki S,Shu H,Yu T,Liang Q,Mao HK,Hemley RJ

    更新日期:2008-11-18 00:00:00

  • The kuru infectious agent is a unique geographic isolate distinct from Creutzfeldt-Jakob disease and scrapie agents.

    abstract::Human sporadic Creutzfeldt-Jakob disease (sCJD), endemic sheep scrapie, and epidemic bovine spongiform encephalopathy (BSE) are caused by a related group of infectious agents. The new U.K. BSE agent spread to many species, including humans, and clarifying the origin, specificity, virulence, and diversity of these agen...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0905825106

    authors: Manuelidis L,Chakrabarty T,Miyazawa K,Nduom NA,Emmerling K

    更新日期:2009-08-11 00:00:00

  • Human-like hyperplastic prostate with low ZIP1 induced solely by Zn deficiency in rats.

    abstract::Prostate cancer is a leading cause of cancer death in men over 50 years of age, and there is a characteristic marked decrease in Zn content in the malignant prostate cells. The cause and consequences of this loss have thus far been unknown. We found that in middle-aged rats a Zn-deficient diet reduces prostatic Zn lev...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1813956115

    authors: Fong LY,Jing R,Smalley KJ,Wang ZX,Taccioli C,Fan S,Chen H,Alder H,Huebner K,Farber JL,Fiehn O,Croce CM

    更新日期:2018-11-20 00:00:00

  • The Order of the Antipode of Finite-dimensional Hopf Algebra.

    abstract::Examples of finite-dimensional Hopf algebras over a field, whose antipodes have arbitrary even orders >/=4 as mappings, are furnished. The dimension of the Hopf algebra is q(n+1), where the antipode has order 2q, q >/= 2, and n is an arbitrary positive integer. The algebras are not semisimple, and neither they nor the...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.68.11.2631

    authors: Taft EJ

    更新日期:1971-11-01 00:00:00

  • Repression of the overproduction of porphyrin precursors in acute intermittent porphyria by intravenous infusions of hematin.

    abstract::In a patient with a severe attack of acute intermittent porphyria, hematin given intravenously caused marked diminution of serum delta-aminolevulinic acid and porphobilinogen. The decline of aminolevulinate was more rapid than that of porphobilinoge. After 2 days of hematin administration, about 5 days were required f...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.68.11.2725

    authors: Bonkowsky HL,Tschudy DP,Collins A,Doherty J,Bossenmaier I,Cardinal R,Watson CJ

    更新日期:1971-11-01 00:00:00

  • Long-distance lateral diffusion of human Rad51 on double-stranded DNA.

    abstract::Rad51 is the primary eukaryotic recombinase responsible for initiating DNA strand exchange during homologous recombination. Although the subject of intense study for over a decade, many molecular details of the reactions promoted by Rad51 and related recombinases remain unknown. Using total internal reflection fluores...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0508366103

    authors: Granéli A,Yeykal CC,Robertson RB,Greene EC

    更新日期:2006-01-31 00:00:00

  • The role of the glycocalyx in reorganization of the actin cytoskeleton under fluid shear stress: a "bumper-car" model.

    abstract::We propose a conceptual model for the cytoskeletal organization of endothelial cells (ECs) based on a major dichotomy in structure and function at basal and apical aspects of the cells. Intracellular distributions of filamentous actin (F-actin), vinculin, paxillin, ZO-1, and Cx43 were analyzed from confocal micrograph...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0407474101

    authors: Thi MM,Tarbell JM,Weinbaum S,Spray DC

    更新日期:2004-11-23 00:00:00

  • Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage.

    abstract::A series of monoclonal antibodies was used to define three discrete stages of human intrathymic T-cell differentiation. The earliest stage was confined to <10% of thymocytes, which were.reactive with both OKT9 and OKT10. Subsequently, approximately 70% of human thymocytes acquired a thymocyte-restricted antigen, OKT6,...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.77.3.1588

    authors: Reinherz EL,Kung PC,Goldstein G,Levey RH,Schlossman SF

    更新日期:1980-03-01 00:00:00

  • Membrane curvature underlies actin reorganization in response to nanoscale surface topography.

    abstract::Surface topography profoundly influences cell adhesion, differentiation, and stem cell fate control. Numerous studies using a variety of materials demonstrate that nanoscale topographies change the intracellular organization of actin cytoskeleton and therefore a broad range of cellular dynamics in live cells. However,...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1910166116

    authors: Lou HY,Zhao W,Li X,Duan L,Powers A,Akamatsu M,Santoro F,McGuire AF,Cui Y,Drubin DG,Cui B

    更新日期:2019-11-12 00:00:00

  • Regulation of p53 tetramerization and nuclear export by ARC.

    abstract::Inactivation of the transcription factor p53 is central to carcinogenesis. Yet only approximately one-half of cancers have p53 loss-of-function mutations. Here, we demonstrate a mechanism for p53 inactivation by apoptosis repressor with caspase recruitment domain (ARC), a protein induced in multiple cancer cells. The ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0710017104

    authors: Foo RS,Nam YJ,Ostreicher MJ,Metzl MD,Whelan RS,Peng CF,Ashton AW,Fu W,Mani K,Chin SF,Provenzano E,Ellis I,Figg N,Pinder S,Bennett MR,Caldas C,Kitsis RN

    更新日期:2007-12-26 00:00:00

  • Evidence from disruption of the lmcpb gene array of Leishmania mexicana that cysteine proteinases are virulence factors.

    abstract::The mammalian form of the protozoan parasite Leishmania mexicana contains high activity of a cysteine proteinase (LmCPb) encoded on a tandem array of 19 genes (lmcpb). Homozygous null mutants for lmcpb have been produced by targeted gene disruption. All life-cycle stages of the mutant can be cultured in vitro, demonst...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.12.6008

    authors: Mottram JC,Souza AE,Hutchison JE,Carter R,Frame MJ,Coombs GH

    更新日期:1996-06-11 00:00:00

  • Genetic evidence that Acanthamoeba myosin I is a true myosin.

    abstract::Acanthamoeba castellanii contains two enzymes, myosins IA and IB, that exhibit the catalytic properties of a myosin but possess very unusual physical properties, the most striking of which are their single, low molecular weight heavy chain, their globular shape, and their inability to form bipolar filaments. We have n...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.13.4655

    authors: Hammer JA 3rd,Jung G,Korn ED

    更新日期:1986-07-01 00:00:00

  • Material-based deployment enhances efficacy of endothelial progenitor cells.

    abstract::Cell-based therapies are attractive for revascularizing and regenerating tissues and organs, but clinical trials of endothelial progenitor cell transplantation have not resulted in consistent benefit. We propose a different approach in which a material delivery system is used to create a depot of vascular progenitor c...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0803873105

    authors: Silva EA,Kim ES,Kong HJ,Mooney DJ

    更新日期:2008-09-23 00:00:00

  • Inverse modulation of plant immune and brassinosteroid signaling pathways by the receptor-like cytoplasmic kinase BIK1.

    abstract::Maintaining active growth and effective immune responses is often costly for a living organism to survive. Fine-tuning the shared cross-regulators is crucial for metazoans and plants to make a trade-off between growth and immunity. The Arabidopsis regulatory receptor-like kinase BAK1 complexes with the receptor kinase...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1302154110

    authors: Lin W,Lu D,Gao X,Jiang S,Ma X,Wang Z,Mengiste T,He P,Shan L

    更新日期:2013-07-16 00:00:00

  • RNA polymerase idling and clearance in gal promoters: use of supercoiled minicircle DNA template made in vivo.

    abstract::We have developed an in vivo system to engender supercoiled "minicircle" DNA containing a single promoter by using the integrative recombination system of bacteriophage lambda. The resulting minicircle templates allow quantitative analysis of the stages of transcription initiation from a promoter, including synthesis ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.2.472

    authors: Choy HE,Adhya S

    更新日期:1993-01-15 00:00:00

  • Structure, function, and evolution of transient and obligate protein-protein interactions.

    abstract::Recent analyses of high-throughput protein interaction data coupled with large-scale investigations of evolutionary properties of interaction networks have left some unanswered questions. To what extent do protein interactions act as constraints during evolution of the protein sequence? How does the type of interactio...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0502667102

    authors: Mintseris J,Weng Z

    更新日期:2005-08-02 00:00:00