المؤلفون: Kun-Liang Guan, Da-Hye Lee, Ja Hyun Koo, Cun-Yu Wang, Dae-Sik Lim, Di Yang, Steven W. Plouffe, Zhipeng Meng

المصدر: Genes Dev
Genes & development, vol 34, iss 1-2

مصطلحات موضوعية: Uveal Neoplasms, medicine.disease_cause, Medical and Health Sciences, Mice, 0302 clinical medicine, Hippo, Transcription (biology), 2.1 Biological and endogenous factors, Aetiology, Promoter Regions, Genetic, Melanoma, Tissue homeostasis, 0303 health sciences, Tumor, Adaptor Proteins, Genes, fos, Organ Size, Biological Sciences, Cell biology, Gene Expression Regulation, Neoplastic, Liver, 030220 oncology & carcinogenesis, Stem Cell Research - Nonembryonic - Non-Human, bilirubin, Biotechnology, Research Paper, c-fos, fos, Biology, liver, Cell Line, Promoter Regions, 03 medical and health sciences, hepatomegaly, Rare Diseases, Genetic, Cell Line, Tumor, Genetics, medicine, cancer, Animals, Humans, Transcription factor, Adaptor Proteins, Signal Transducing, Cell Proliferation, 030304 developmental biology, Neoplastic, Hippo signaling pathway, Cell growth, Human Genome, Psychology and Cognitive Sciences, Signal Transducing, YAP-Signaling Proteins, Promoter, Stem Cell Research, Transcription Factor AP-1, HEK293 Cells, Gene Expression Regulation, Genes, Transcriptional Coactivator with PDZ-Binding Motif Proteins, Cancer cell, Trans-Activators, Mitogens, Carcinogenesis, Gene Deletion, Transcription Factors, Developmental Biology

الوصف: Yes-associated protein (YAP) and its homolog transcriptional coactivator with PDZ-binding motif (TAZ) are key effectors of the Hippo pathway to control cell growth and organ size, of which dysregulation yields to tumorigenesis or hypertrophy. Upon activation, YAP/TAZ translocate into the nucleus and bind to TEAD transcription factors to promote transcriptional programs for proliferation or cell specification. Immediate early genes, represented by AP-1 complex, are rapidly induced and control later-phase transcriptional program to play key roles in tumorigenesis and organ maintenance. Here, we report that YAP/TAZ directly promote FOS transcription that in turn contributes to the biological function of YAP/TAZ. YAP/TAZ bind to the promoter region of FOS to stimulate its transcription. Deletion of YAP/TAZ blocks the induction of immediate early genes in response to mitogenic stimuli. FOS induction contributes to expression of YAP/TAZ downstream target genes. Genetic deletion or chemical inhibition of AP-1 suppresses growth of YAP-driven cancer cells, such as Lats1/2-deficient cancer cells as well as Gαq/11 mutated uveal melanoma. Furthermore, AP-1 inhibition almost completely abrogates the hepatomegaly induced by YAP overexpression. Our findings reveal a feed-forward interplay between immediate early transcription of AP-1 and Hippo pathway function.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b4932433e75f0c2b2317020a98402584Test
https://doi.org/10.1101/gad.331546.119Test

المؤلفون: Kun-Liang Guan, Zhipeng Meng, Toshiro Moroishi

المصدر: Genes & development, vol 30, iss 1

مصطلحات موضوعية: Enzymologic, TAZ, 0301 basic medicine, endocrine system, animal structures, 1.1 Normal biological development and functioning, LATS, Review, Protein Serine-Threonine Kinases, Biology, Medical and Health Sciences, Gene Expression Regulation, Enzymologic, 03 medical and health sciences, Underpinning research, Cell polarity, Genetics, Animals, Humans, TEAD1, Transcription factor, MST, Hippo signaling pathway, MAP4K, TEAD, Cell growth, Psychology and Cognitive Sciences, fungi, Biological Sciences, Actin cytoskeleton, Cell biology, body regions, Drosophila melanogaster, 030104 developmental biology, Gene Expression Regulation, Hippo signaling, sense organs, YAP, Generic health relevance, Signal transduction, Transcription Factors, Signal Transduction, Biotechnology, Developmental Biology

الوصف: The Hippo pathway was initially identified in Drosophila melanogaster screens for tissue growth two decades ago and has been a subject extensively studied in both Drosophila and mammals in the last several years. The core of the Hippo pathway consists of a kinase cascade, transcription coactivators, and DNA-binding partners. Recent studies have expanded the Hippo pathway as a complex signaling network with >30 components. This pathway is regulated by intrinsic cell machineries, such as cell–cell contact, cell polarity, and actin cytoskeleton, as well as a wide range of signals, including cellular energy status, mechanical cues, and hormonal signals that act through G-protein-coupled receptors. The major functions of the Hippo pathway have been defined to restrict tissue growth in adults and modulate cell proliferation, differentiation, and migration in developing organs. Furthermore, dysregulation of the Hippo pathway leads to aberrant cell growth and neoplasia. In this review, we focus on recent developments in our understanding of the molecular actions of the core Hippo kinase cascade and discuss key open questions in the regulation and function of the Hippo pathway.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2c77ed0bc1658205e4cb9f9a7e594dedTest
https://doi.org/10.1101/gad.274027.115Test