PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 15108809

HIF-1 and hypoxic response: the plot thickens.

Lorenz Poellinger·Randall S Johnson
View original source ↗Export metadata ↓

Abstract

Hypoxia, or lowered physiological oxygenation, is a component of many diseases. The response to decreased oxygen tensions is also an essential aspect of normal development and physiology. The hypoxic response is chiefly mediated by a single transcription factor--the hypoxia-inducible transcription factor HIF-1. The central role played by HIF-1 in hypoxia-induced transcription has made the focus of intense investigation by biologists from a wide range of disciplines. Recent developments have produced fundamental advances in our understanding of both the regulation and function of this response pathway in animals, and illustrated the potential for manipulation of the pathway for therapeutic purposes.

Explore related subjects

DNA-Binding ProteinsErythropoiesisHumansHypoxiaHypoxia-Inducible Factor 1Hypoxia-Inducible Factor 1, alpha SubunitNuclear ProteinsProtein Processing, Post-TranslationalTranscription FactorsJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Lorenz Poellinger, Randall S Johnson. 2004. HIF-1 and hypoxic response: the plot thickens.. https://doi.org/10.1016/j.gde.2003.12.006

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2026

Cellular modifiers of TDP-43 phase transition and cytoplasmic aggregation.

RNA-binding protein TAR DNA-binding protein 43 (TDP-43) can form liquid-like nuclear assemblies whose phase behavior is thought to influence its aggregation propensity and neurotoxic activity. The mechanisms that govern the liquid-to-solid phase transition of TDP-43 remain poorly defined. Here, we combined chemical and genome-wide genetic screens to identify cellular factors that modulate the phase behavior of an RNA-binding-defective TDP-43 mutant. Our screens uncovered multiple cellular processes, including RNA splicing, protein translation, proteostasis imbalance, and nuclear export as TDP-43 phase regulators. We also developed a semi-permeabilized cell system that partially recapitulates the TDP-43 phase transition in vitro, and showed that nuclear export inhibition reshapes the nuclear environment to favor RNA-dependent liquid-liquid phase separation (LLPS) of TDP-43, which mitigates its aggregation. Nuclear export inhibition in a brain organoid model bearing an ALS-associated mutation reduces pathogenic phospho-TDP-43 accumulation. These findings identify multiple modulators of TDP-43 phase transitions in a sensitized model system and establish a framework for further dissecting the link between nuclear transport and TDP-43 phase dynamics.

DNA-Binding Proteins↗
PubMed2024

The Lrs14 family of DNA-binding proteins as nucleoid-associated proteins in the Crenarchaeal order Sulfolobales.

Organization of archaeal chromatin combines bacterial, eukaryotic, and unique characteristics. Many archaeal lineages harbor a wide diversity of small and highly expressed nucleoid-associated proteins, which are involved in DNA structuring. In Sulfolobales, representing model organisms within the Crenarchaeota, Sul7d, Cren7, Sul10a, and Sul12a are well-characterized nucleoid-associated proteins. Here, we combine evidence that the Lrs14 family of DNA binders is part of the repertoire of nucleoid-associated proteins in Sulfolobales. Lrs14-encoding genes are widespread within genomes of different members of the Sulfolobales, typically encoded as four to nine homologs per genome. The Lrs14 proteins harbor a winged helix-turn-helix DNA-binding domain and are typified by a coiled-coil dimerization. They are characterized by distinct sequence- and structure-based features, including redox-sensitive motifs and residues targeted for posttranslational modification, allowing a further classification of the family into five conserved clusters. Lrs14-like proteins have unique DNA-organizing properties. By binding to the DNA nonsequence specifically and in a highly cooperative manner, with a slight preference for AT-rich promoter regions, they introduce DNA kinks and are able to affect transcription of adjacent transcription units either positively or negatively. Genes encoding Lrs14-type proteins display considerable differential expression themselves in response to various stress conditions, with certain homologs being specific to a particular stressor. Taken together, we postulate that members of the Lrs14 family can be considered nucleoid-associated proteins in Sulfolobales, combining a DNA-structuring role with a global gene expression role in response to stress conditions.

DNA-Binding Proteins↗
PubMed2007

Directional mRNA transport in eukaryotes: lessons from yeast.

In eukaryotes, developmental processes and cell differentiation, as well as basic cellular functions require the propagation of information in an asymmetric manner. Localization of mRNA is a key mechanism to establish asymmetric cell fate. The first part of this review provides an overview of our current knowledge of motor protein-dependent mRNA transport in eukaryotes. The second part provides a more detailed description of the most comprehensively studied mRNA translocation complex to date: the ASH1 messenger ribonucleoprotein particle (mRNP) from Saccharomyces cerevisiae. During budding of yeast, the ASH1 mRNP transports cell fate determinants exclusively into the daughter cell. The core factors of the ASH1 mRNP have been identified, their interactions have been studied in detail, and the three-dimensional structure of its mRNA-binding protein, She2p, has been determined. Because no other mRNP has been studied in such detail, the ASH1 mRNP could serve as a model for asymmetric segregation of cell fate determinants in higher eukaryotes.

DNA-Binding Proteins↗