The MITF, TFEB, TFE3 and TFEC (MiT-TFE) proteins belong to the basic helix-loop-helix family of leucine zipper transcription factors. MITF is crucial for melanocyte development and differentiation, and has been termed a lineage-specific oncogene in melanoma. The three related proteins MITF, TFEB and TFE3 have been shown to be involved in the biogenesis and function of lysosomes and autophagosomes, regulating cellular clearance pathways. Here we investigated the cross-regulatory relationship of MITF and TFEB in melanoma cells. Like MITF, the TFEB and TFE3 genes are expressed in melanoma cells as well as in melanoma tumors, albeit at lower levels. We show that the MITF and TFEB proteins, but not TFE3, directly affect each other's mRNA and protein expression. In addition, the subcellular localization of MITF and TFEB is subject to regulation by the mTOR signaling pathway, which impacts their cross-regulatory relationship at the transcriptional level. Our work shows that the relationship between MITF and TFEB is multifaceted and that the cross-regulatory interactions of these factors need to be taken into account when considering pathways regulated by these proteins.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470386 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238546 | PLOS |
Within cells multiple related transcription factors targeting the same sequences may co-exist, leading to potential regulatory cooperativity, redundancy or competition. Yet the differential roles and biological functions of co-targeting transcription factors is poorly understood. In melanoma, three highly-related transcription factors are co-expressed: The mTORC1-regulated TFEB and TFE3, that are key effectors of a wide range of metabolic and microenvironmental cues; and MITF, that controls melanoma phenotypic identity.
View Article and Find Full Text PDFImmunity
December 2024
Department of Thoracic Surgery of Sir Run Run Shaw Hospital, and Department of Biochemistry, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, China. Electronic address:
Induction of autophagy is an ancient function of the cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway through which autophagic cargoes are delivered to lysosomes for degradation. However, whether lysosome function is also modulated by the cGAS-STING pathway remains unknown. Here, we discovered that the cGAS-STING pathway upregulated lysosomal activity by stimulating lysosome biogenesis independently of the downstream protein kinase TANK-binding kinase 1 (TBK1).
View Article and Find Full Text PDFHeliyon
November 2024
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, United Kingdom.
The major cause of death in cancer patients is a combination of metastatic dissemination combined with therapy resistance. Over recent years, intratumour phenotypic heterogeneity arising from the bi-directional interplay between plastic cancer cells and the microenvironment has been identified as key to disease progression. Most notably metastatic outgrowth and resistance to targeted therapies are frequently associated with activity of mTORC1, a key metabolic hub that promotes protein synthesis and proliferation in the presence of nutrients.
View Article and Find Full Text PDFJ Bacteriol
August 2024
Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Unlabelled: is a highly infectious, Gram-negative, obligate intracellular bacterium and the causative agent of human Q fever. The Containing Vacuole (CCV) is a modified phagolysosome that forms through fusion with host endosomes and lysosomes. While an initial acidic pH < 4.
View Article and Find Full Text PDFTrends Cell Biol
May 2024
Institute of Biophysics, Johannes Kepler University Linz, Linz, Austria.
Calcium (Ca) plays a pivotal role in cellular signal transmission by triggering downstream signaling in response to an increase in the cytosolic Ca concentration. Intracellular organelles serve as Ca stores that induce differently shaped Ca signals. We discuss a study by Yuan et al.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!