The TIP60 Complex Is a Conserved Coactivator of HIF1A

Perez-Perri, Joel I.; Dengler, Veronica L.; Audetat, K. Audrey; Pandey, Ahwan; Bonner, Elizabeth; Urh, Marjeta; Méndez, Jacqui; Daniels, Danette L.; Wappner, Pablo; Galbraith, Matthew D.; Espinosa, Joaquín M.

doi:10.1016/j.celrep.2016.05.082

Cited by 85 publications

(93 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, in certain contexts CDK8 has been described as a tumor suppressor (Clark et al, 2015; Gu et al, 2013; Li et al, 2014). We and others have shown that CDK8 is a positive regulator of transcriptional programs that drive the proliferation and survival of cancer cells, including those controlled by Wnt/β-catenin (Firestein et al, 2008), ERK/MAP kinase signaling (Donner et al, 2010), and HIF1A (Galbraith et al, 2013; Perez-Perri et al, 2016). Thus, it is possible that pharmacological inhibition of CDK8 could have therapeutic value by simultaneously decreasing the activity of multiple oncogenic pathways.…”

Section: Introductionmentioning

confidence: 99%

CDK8 Kinase Activity Promotes Glycolysis

et al. 2017

Self Cite

View full text Add to dashboard Cite

SUMMARY Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancerous tissues. Despite its importance in cancer development, our understanding of mechanisms driving this form of metabolic reprogramming is incomplete. We report here an analysis of colorectal cancer cells engineered to carry a single point mutation in the active site of the Mediator-associated kinase CDK8, creating hypomorphic alleles sensitive to bulky ATP analogs. Transcriptome analysis revealed CDK8 kinase activity is required for expression of many components of the glycolytic cascade. CDK8 inhibition impairs glucose transporter expression, glucose uptake, glycolytic capacity and reserve, as well as cell proliferation and anchorage independent growth, both in normoxia and hypoxia. Importantly, CDK8 impairment sensitizes cells to pharmacological glycolysis inhibition, a result reproduced with Senexin A, a dual inhibitor of CDK8/CDK19. Altogether, these results contribute to our understanding of CDK8 as an oncogene and justify investigations to target CDK8 in highly glycolytic tumors.

show abstract

Section: Introductionmentioning

confidence: 99%

CDK8 Kinase Activity Promotes Glycolysis

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Similarly, the histone acetyltransferase TIP60 was recently reported to enhance HIF-1 transcriptional activity and activate about 25% of HIF-1 downstream target genes in colorectal cancer HCT116 cells [30]. TIP60 is recruited by HIF-1α to the hypoxia response element of the HIF-1 target gene ANKRD37 .…”

Section: Regulation Of Hif Transcriptional Activity By Epigenetic Wrimentioning

confidence: 99%

Epigenetic regulators: multifunctional proteins modulating hypoxia-inducible factor-α protein stability and activity

Luo

Wang

2017

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

The hypoxia-inducible factor (HIF) is a heterodimeric transcription factor governing a transcriptional program in response to reduced O2 availability in metazoans. It contributes to physiology and pathogenesis of many human diseases through its downstream target genes. Emerging studies have shown that the transcriptional activity of HIF is highly regulated at multiple levels and the epigenetic regulators are essential for HIF-mediated transactivation. In this review, we will discuss the comprehensive regulation of HIF transcriptional activity by different types of epigenetic regulators.

show abstract

“…In addition, the TIP60 complex is required for HIF1-dependent gene expression in fly cells and embryos, as well as colorectal cancer cells. TIP60 is recruited by HIF1 to chromatin during hypoxia and functions as a coactivator of HIF1 action by recruiting RNA-Polymerase II onto chromatin [186]. Finally, Musashi (Msi, dMsi in Drosophila) represses sima mRNA translation by binding an Msi-binding element within the 3′ UTR of the sima transcript.…”

Section: Upstream Regulators Of Hif-1α/sima In Hypoxiamentioning

confidence: 99%

“…Further work on Sima regulators has uncovered several modifiers of Sima function in hypoxia in Drosophila, such as the microRNA miR-190, the TIP60 chromatin remodeling complex and the RNA-binding protein Musashi [184][185][186] (Figure 2). miR-190 acts as a positive regulator of the hypoxic response by targeting directly the propyl-4-hydroxylase Fga, which is the principal negative regulator of Sima.…”

Section: Upstream Regulators Of Hif-1α/sima In Hypoxiamentioning

confidence: 99%

“…The ago1 (argonaute 1) gene, which has a critical role in microRNA silencing processes, was also identified in this screen as a regulator of Sima in hypoxia. Given the involvement of Ago1 in Sima regulation, the authors went further to show that the microRNA pathway has a central role in HIF-dependent transcription, and also that Sima mRNA stabilization has a critical role in the Drosophila response to hypoxia [183].Further work on Sima regulators has uncovered several modifiers of Sima function in hypoxia in Drosophila, such as the microRNA miR-190, the TIP60 chromatin remodeling complex and the RNA-binding protein Musashi [184][185][186] (Figure 2). miR-190 acts as a positive regulator of the hypoxic response by targeting directly the propyl-4-hydroxylase Fga, which is the principal negative regulator of Sima.…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Hypoxia-Inducible Factor-1α in Angiogenesis and Cancer: Insights from the Drosophila Model

Tamamouna¹,

Pitsouli²

2018

Gene Expression and Regulation in Mammalian Cells - Transcription Toward the Establishment of Novel Therapeutics

View full text Add to dashboard Cite

The hypoxia-inducible factor-1α (HIF-1α) is an evolutionarily conserved transcription factor with prominent roles in the hypoxic response, cell survival, angiogenesis and cancer. HIF-1α functions as a sensor of molecular oxygen: in the presence of oxygen, it is degraded by the proteasome, whereas in reduced oxygen tensions, it heterodimerizes with the constitutively expressed HIF-1b subunit forming the functional HIF1 transcription factor, which enters the nucleus to control expression of hypoxia-inducible genes. Since HIF-1α has been found upregulated in several cancers, it has attracted a lot of clinical interest, because it represents an interesting candidate for pharmacological chemotherapy interventions. In this chapter, we discuss our current knowledge on the HIF1 transcription factors and their major roles in development, physiology, angiogenesis and cancer using examples of recent studies in the model organism Drosophila melanogaster. Given the striking functional conservation between the mammalian and fruit fly HIF-1α, we expect that future studies in the Drosophila model will not only expand our knowledge on the basic HIF1 biology, but they will also pinpoint conserved molecular regulators of HIF1 that might lead to the discovery of novel cancer therapeutics.Keywords: hypoxia, tumorigenesis, Warburg effect, metabolism, tracheogenesis, inflammation, Drosophila 1. HIF-1α in mammalian angiogenesis, inflammation and cancer Oxygen is required for survival of all animalsOxygen (O 2 ) is the main ingredient of the atmospheric air and is required for the survival of all living organisms. It is also present in the seas and oceans, and it is necessary for survival of all aquatic living organisms. Oxygen accumulated on Earth's atmosphere about 2.5 billion © 2018 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.years ago [1]. However, it was discovered only 245 years ago, by the chemist Carl Wilhelm Scheele [2]. Its main role in the survival of animals derives from its utilization during cellular respiration. Specifically, oxygen is involved in oxidative phosphorylation, the process that transfers the chemical energy stored in carbon bonds to the phosphate bonds of Adenosine Tri-Phosphate (ATP), which is the main energy carrier in all cell types of living organisms [3]. In addition, oxygen is the main component of ATP production, because it is the final electron acceptor of the respiratory chain. Oxygen-electron reaction leads to the release of reactive oxygen species (ROS), which, when accumulated, results in oxidative stress and eventually cell death [4,5]. Oxygen is necessary as an energy substrate, and the danger of oxidative damage needs to be kept at equilibrium. Therefore, oxygen homeostasis is critical for all cellular processes, and its intermittent supply resul...

show abstract

The TIP60 Complex Is a Conserved Coactivator of HIF1A

Cited by 85 publications

References 49 publications

CDK8 Kinase Activity Promotes Glycolysis

CDK8 Kinase Activity Promotes Glycolysis

Epigenetic regulators: multifunctional proteins modulating hypoxia-inducible factor-α protein stability and activity

The Hypoxia-Inducible Factor-1α in Angiogenesis and Cancer: Insights from the Drosophila Model

Contact Info

Product

Resources

About