scholarly journals The Role of Hypoxia-Inducible Factor Post-Translational Modifications in Regulating its Localisation, Stability and Activity

2020 ◽  
Author(s):  
Adam Albanese ◽  
Leonard A. Daly ◽  
Daniela Mennerich ◽  
Thomas Kietzmann ◽  
Violaine Sée
Keyword(s):  
Transcription Factors ◽  
Crucial Role ◽  
Hypoxia Inducible Factor ◽  
Oxygen Availability ◽  
Signalling Pathway ◽  
Hypoxia Inducible Factors ◽  
Cellular Homeostasis ◽  
Post Translational Modifications ◽  
Alpha Subunits

The hypoxia signalling pathway enables adaptation of cells to decreased oxygen availability. When oxygen becomes limiting, the central transcription factors of the pathway, hypoxia-inducible factors (HIFs), are stabilised and activated to induce the expression of hypoxia-regulated genes, thereby maintaining cellular homeostasis. Whilst hydroxylation has been thoroughly described as the major and canonical modification of the HIF-α subunits, regulating both HIF stability and activity, a range of other post-translational modifications decorating the entire protein play also a crucial role in altering HIF localisation, stability, and activity. These modifications, their conservation throughout evolution and their effects on HIF-dependent signalling are discussed in this review.

scholarly journals The Role of Hypoxia-Inducible Factor Post-Translational Modifications in Regulating Its Localisation, Stability, and Activity

2020 ◽  
Vol 22 (1) ◽  
pp. 268
Author(s):  
Adam Albanese ◽  
Leonard A. Daly ◽  
Daniela Mennerich ◽  
Thomas Kietzmann ◽  
Violaine Sée
Keyword(s):  
Transcription Factors ◽  
Crucial Role ◽  
Hypoxia Inducible Factor ◽  
Oxygen Availability ◽  
Signalling Pathway ◽  
Hypoxia Inducible Factors ◽  
Cellular Homeostasis ◽  
Post Translational Modifications ◽  
Α Subunits

The hypoxia signalling pathway enables adaptation of cells to decreased oxygen availability. When oxygen becomes limiting, the central transcription factors of the pathway, hypoxia-inducible factors (HIFs), are stabilised and activated to induce the expression of hypoxia-regulated genes, thereby maintaining cellular homeostasis. Whilst hydroxylation has been thoroughly described as the major and canonical modification of the HIF-α subunits, regulating both HIF stability and activity, a range of other post-translational modifications decorating the entire protein play also a crucial role in altering HIF localisation, stability, and activity. These modifications, their conservation throughout evolution, and their effects on HIF-dependent signalling are discussed in this review.

scholarly journals Traumatic glioblastoma: commentary and suggested mechanism

2018 ◽  
Vol 46 (6) ◽  
pp. 2170-2176
Author(s):  
Nissim Ohana ◽  
Daniel Benharroch ◽  
Dimitri Sheinis ◽  
Abraham Cohen
Keyword(s):  
Traumatic Brain Injury ◽  
Transcription Factors ◽  
Brain Injury ◽  
Brain Injuries ◽  
Hypoxia Inducible Factor ◽  
Subsequent Development ◽  
Factors Associated ◽  
The Relationship

The role of head trauma in the development of glioblastoma is highly controversial and has been minimized since first put forward. This is not unexpected because skull injuries are overwhelmingly more common than glioblastoma. This paper presents a commentary based on the contributions of James Ewing, who established a major set of criteria for the recognition of an official relationship between trauma and cancer. Ewing’s criteria were very stringent. The scholars who succeeded Ewing have facilitated the characterization of traumatic brain injuries since the introduction of computed tomography and magnetic resonance imaging. Discussions of the various criteria that have since developed are now being conducted, and those of an unnecessarily limiting nature are being highlighted. Three transcription factors associated with traumatic brain injury have been identified: p53, hypoxia-inducible factor-1α, and c-MYC. A role for these three transcription factors in the relationship between traumatic brain injury and glioblastoma is suggested; this role may support a cause-and-effect link with the subsequent development of glioblastoma.

scholarly journals The Canonical Wnt Pathway as a Key Regulator in Liver Development, Differentiation and Homeostatic Renewal

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1163
Author(s):  
Sebastian L. Wild ◽  
Aya Elghajiji ◽  
Carmen Grimaldos Rodriguez ◽  
Stephen D. Weston ◽  
Zoë D. Burke ◽  
...  
Keyword(s):  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Signalling Pathway ◽  
Fate Specification ◽  
Cellular Processes ◽  
Recent Developments ◽  
Body Patterning ◽  
Important Regulator ◽  
Canonical Wnt

The canonical Wnt (Wnt/β-catenin) signalling pathway is highly conserved and plays a critical role in regulating cellular processes both during development and in adult tissue homeostasis. The Wnt/β-catenin signalling pathway is vital for correct body patterning and is involved in fate specification of the gut tube, the primitive precursor of liver. In adults, the Wnt/β-catenin pathway is increasingly recognised as an important regulator of metabolic zonation, homeostatic renewal and regeneration in response to injury throughout the liver. Herein, we review recent developments relating to the key role of the pathway in the patterning and fate specification of the liver, in the directed differentiation of pluripotent stem cells into hepatocytes and in governing proliferation and zonation in the adult liver. We pay particular attention to recent contributions to the controversy surrounding homeostatic renewal and proliferation in response to injury. Furthermore, we discuss how crosstalk between the Wnt/β-catenin and Hedgehog (Hh) and hypoxia inducible factor (HIF) pathways works to maintain liver homeostasis. Advancing our understanding of this pathway will benefit our ability to model disease, screen drugs and generate tissue and organ replacements for regenerative medicine.

scholarly journals Regulation of WASP/WAVE proteins

2004 ◽  
Vol 166 (7) ◽  
pp. 957-962 ◽  
Author(s):  
Guillaume Bompard ◽  
Emmanuelle Caron
Keyword(s):  
Crucial Role ◽  
Actin Polymerization ◽  
Post Translational Modifications ◽  
Wasp Family Proteins

Despite their homology, the regulation of WASP and WAVE, activators of Arp2/3-dependent actin polymerization, has always been thought to be different. Several recent studies have revealed new aspects of their regulation, highlighting its complexity and the crucial role of post-translational modifications. New data also suggest additional functions for WASP family proteins, pushing us to reconsider existing models.

scholarly journals Different roles for two enhancer domains in the organ- and age-specific pattern of polyomavirus replication in the mouse.

1992 ◽  
Vol 12 (8) ◽  
pp. 3628-3635 ◽  
Author(s):  
A Amalfitano ◽  
L G Martin ◽  
M M Fluck
Keyword(s):  
Transcription Factors ◽  
In Situ Hybridization ◽  
Mammary Gland ◽  
Crucial Role ◽  
Specific Pattern ◽  
Neonatal Stage ◽  
Murine Polyomavirus ◽  
A Domains

Viral replication in mice infected with murine polyomavirus strains with novel enhancer rearrangements was analyzed by direct in situ hybridization of whole mouse sections and by hybridization of nucleic acids extracted from a specific set of organs. The enhancer rearrangements included a deletion of the B domain as well as duplications within the A domain. Comparisons between enhancer variants demonstrate that the B domain plays an important role in replication in most organs, in particular in the kidney, at the neonatal stage (days 0 to 7 postbirth). In contrast, the B domain is not required in those organs which can sustain replication in the adult, i.e. mammary gland, skin, and bone (class I organs [J. J. Wirth, A. Amalfitano, R. Gross, M. B. A. Oldstone, and M. M. Fluck, J. Virol. 66:3278-3286, 1992]). Altogether, the results suggest that the B and A domains mediate very different functions in infection of mice, controlling the acute and persistent phases of infection, respectively. A model of mouse infection based on the crucial role of differentially expressed host transcription factors is presented.

Organization of chromatin in cancer cells: role of signalling pathways

1999 ◽  
Vol 77 (4) ◽  
pp. 265-275 ◽  
Author(s):  
J R Davie ◽  
S K Samuel ◽  
V A Spencer ◽  
L T Holth ◽  
D N Chadee ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Nuclear Matrix ◽  
Nuclear Dna ◽  
Mapk Pathway ◽  
Signalling Pathway ◽  
Signalling Pathways ◽  
Chemical Signalling

The role of mechanical and chemical signalling pathways in the organization and function of chromatin is the subject of this review. The mechanical signalling pathway consists of the tissue matrix system that links together the three-dimensional skeletal networks, the extracellular matrix, cytoskeleton, and nuclear matrix. Intermediate filament proteins are associated with nuclear DNA, suggesting that intermediate filaments may have a role in the organization of chromatin. In human hormone-dependent breast cancer cells, the interaction between cytokeratins and chromatin is regulated by estrogens. Transcription factors, histone acetyltransferases, and histone deacetylases, which are associated with the nuclear matrix, are components of the mechanical signalling pathway. Recently, we reported that nuclear matrix-bound human and chicken histone deacetylase 1 is associated with nuclear DNA in situ, suggesting that histone deacetylase has a role in the organization of nuclear DNA. Chemical signalling pathways such as the Ras/mitogen-activated protein kinase (Ras/MAPK) pathway stimulate the activity of kinases that modify transcription factors, nonhistone chromosomal proteins, and histones. The levels of phosphorylated histones are increased in mouse fibroblasts transformed with oncogenes, the products of which stimulate the Ras/MAPK pathway. Histone phosphorylation may lead to decondensation of chromatin, resulting in aberrant gene expression.Key words: histone acetylation, histone phosphorylation, nuclear matrix, cytoskeleton, histone deacetylase, cancer.

scholarly journals The evolving role of ribosomes in the regulation of protein synthesis

2020 ◽  
Author(s):  
Karolina Gościńska ◽  
Ulrike Topf
Keyword(s):  
Protein Synthesis ◽  
Crucial Role ◽  
Protein Production ◽  
Protein Composition ◽  
Disease Development ◽  
Target Specificity ◽  
Cellular Homeostasis ◽  
Multiple Levels ◽  
Polypeptide Chains

Maintenance of the cellular homeostasis is firmly linked with protein synthesis. Therefore, it is tightly controlled at multiple levels. An advancement in quantitative techniques, mainly over the last decade, shed new light on the regulation of protein production, which pointed the ribosome as a new player. Ribosomes are macromolecular machines that synthesize polypeptide chains using mRNA as a template. The enormous complexity of ribosomes provides many possibilities of changes in their composition and consecutively in their target specificity. However, it is not clear how this specialization is enforced by the cell and which stimuli provoke that diversity. This review presents an overview of currently available knowledge about ribosome heterogeneity, focusing on changes in protein composition, and their role in the control of translation specificity. Importantly, besides the potential advantage of ribosome-mediated regulation of protein synthesis, its failure can play a crucial role in disease development.

Different roles for two enhancer domains in the organ- and age-specific pattern of polyomavirus replication in the mouse

1992 ◽  
Vol 12 (8) ◽  
pp. 3628-3635
Author(s):  
A Amalfitano ◽  
L G Martin ◽  
M M Fluck
Keyword(s):  
Transcription Factors ◽  
In Situ Hybridization ◽  
Mammary Gland ◽  
Crucial Role ◽  
Specific Pattern ◽  
Neonatal Stage ◽  
Murine Polyomavirus ◽  
A Domains

Viral replication in mice infected with murine polyomavirus strains with novel enhancer rearrangements was analyzed by direct in situ hybridization of whole mouse sections and by hybridization of nucleic acids extracted from a specific set of organs. The enhancer rearrangements included a deletion of the B domain as well as duplications within the A domain. Comparisons between enhancer variants demonstrate that the B domain plays an important role in replication in most organs, in particular in the kidney, at the neonatal stage (days 0 to 7 postbirth). In contrast, the B domain is not required in those organs which can sustain replication in the adult, i.e. mammary gland, skin, and bone (class I organs [J. J. Wirth, A. Amalfitano, R. Gross, M. B. A. Oldstone, and M. M. Fluck, J. Virol. 66:3278-3286, 1992]). Altogether, the results suggest that the B and A domains mediate very different functions in infection of mice, controlling the acute and persistent phases of infection, respectively. A model of mouse infection based on the crucial role of differentially expressed host transcription factors is presented.

Sign in / Sign up

Export Citation Format

Share Document