Cisplatin-induced regulation of signal transduction pathways and transcription factors in p53-mutated subclone variants of hepatoma cells: Potential application for therapeutic targeting

Abstract Transcriptional regulation, a pivotal biological process by which cells adapt to environmental fluctuations, is achieved by the binding of transcription factors to target sequences in a sequence-specific manner. However, how transcription factors recognize the correct target from amongst the numerous candidates in a genome has not been fully elucidated. We here show that, in the fission-yeast fbp1 gene, when transcription factors bind to target sequences in close proximity, their binding is reciprocally stabilized, thereby integrating distinct signal transduction pathways. The fbp1 gene is massively induced upon glucose starvation by the activation of two transcription factors, Atf1 and Rst2, mediated via distinct signal transduction pathways. Atf1 and Rst2 bind to the upstream-activating sequence 1 region, carrying two binding sites located 45 bp apart. Their binding is reciprocally stabilized due to the close proximity of the two target sites, which destabilizes the independent binding of Atf1 or Rst2. Tup11/12 (Tup-family co-repressors) suppress independent binding. These data demonstrate a previously unappreciated mechanism by which two transcription-factor binding sites, in close proximity, integrate two independent-signal pathways, thereby behaving as a hub for signal integration.

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Effects of heptachlor epoxide on components of various signal transduction pathways important in tumor promotion in mouse hepatoma cells

Toxicology ◽

10.1016/s0300-483x(00)00445-5 ◽

2001 ◽

Vol 160 (1-3) ◽

pp. 139-153 ◽

Cited By ~ 11

Author(s):

Mark E Hansen ◽

Fumio Matsumura

Keyword(s):

Signal Transduction ◽

Tumor Promotion ◽

Hepatoma Cells ◽

Heptachlor Epoxide ◽

Signal Transduction Pathways ◽

Mouse Hepatoma

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S.17.01 Regulation of transcription factors by signal transduction pathways

European Neuropsychopharmacology ◽

10.1016/s0924-977x(97)88412-x ◽

1997 ◽

Vol 7 ◽

pp. S109

Author(s):

M. Yaniv

Keyword(s):

Signal Transduction ◽

Transcription Factors ◽

Signal Transduction Pathways ◽

Regulation Of Transcription

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Insights into Functional Connectivity in Mammalian Signal Transduction Pathways by Pairwise Comparison of Protein Interaction Partners of Critical Signaling Hubs

10.1101/2019.12.30.891200 ◽

2019 ◽

Cited By ~ 1

Author(s):

Chilakamarti V. Ramana

Keyword(s):

Signal Transduction ◽

Transcription Factors ◽

Functional Connectivity ◽

Protein Interaction ◽

Target Genes ◽

Pairwise Comparison ◽

Signal Transduction Pathways ◽

Critical Nodes ◽

Interaction Partners ◽

Signaling Modules

AbstractGrowth factors and cytokines activate signal transduction pathways and regulate gene expression in eukaryotes. Intracellular domains of activated receptors recruit several protein kinases as well as transcription factors that serve as platforms or hubs for the assembly of multi-protein complexes. The signaling hubs involved in a related biologic function often share common interaction proteins and target genes. This functional connectivity suggests that a pairwise comparison of protein interaction partners of signaling hubs and network analysis of common partners and their expression analysis might lead to the identification of critical nodes in cellular signaling. A pairwise comparison of signaling hubs across several related pathways might also reveal novel signaling modules. Analysis of Protein Interaction Connectome by Venn (PIC-VENN) of transcription factors STAT1, STAT3, NFKB1, RELA, FOS and JUN, and their common interaction network suggested that BRCA1 and TSC22D3 function as critical nodes in immune responses by connecting the signaling nodes into signaling modules. Mutations or differential expression levels of these critical nodes in pathological conditions might deregulate signaling pathways and their target genes involved in inflammation. Biological connectivity emerges from the structural connectivity of interaction networks across several signaling hubs in related pathways. Application of PIC-VENN to several signaling hubs might reveal novel nodes and modules that can be targeted to simultaneously activate or inhibit cell signaling in health and disease.

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FoxO Proteins in the Nervous System

Analytical Cellular Pathology ◽

10.1155/2015/569392 ◽

2015 ◽

Vol 2015 ◽

pp. 1-15 ◽

Cited By ~ 11

Author(s):

Kenneth Maiese

Keyword(s):

Signal Transduction ◽

Nervous System ◽

Transcription Factors ◽

Protein Kinase ◽

The Body ◽

Signal Transduction Pathways ◽

Forkhead Transcription Factors ◽

Cell Death Pathways ◽

Neuronal Disease ◽

Inducible Protein

Acute as well as chronic disorders of the nervous system lead to significant morbidity and mortality for millions of individuals globally. Given the ability to govern stem cell proliferation and differentiated cell survival, mammalian forkhead transcription factors of the forkhead box class O (FoxO) are increasingly being identified as potential targets for disorders of the nervous system, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and auditory neuronal disease. FoxO proteins are present throughout the body, but they are selectively expressed in the nervous system and have diverse biological functions. The forkhead O class transcription factors interface with an array of signal transduction pathways that include protein kinase B (Akt), serum- and glucocorticoid-inducible protein kinase (SgK), IκB kinase (IKK), silent mating type information regulation 2 homolog 1 (S. cerevisiae) (SIRT1), growth factors, and Wnt signaling that can determine the activity and integrity of FoxO proteins. Ultimately, there exists a complex interplay between FoxO proteins and their signal transduction pathways that can significantly impact programmed cell death pathways of apoptosis and autophagy as well as the development of clinical strategies for the treatment of neurodegenerative disorders.

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