Posttranslational Modifications of p53: Upstream Signaling Pathways

2007 ◽  
pp. 95-114
Author(s):  
Carl W. Anderson ◽  
Ettore Appella
Keyword(s):  
Signaling Pathways ◽  
Posttranslational Modifications

scholarly journals Epigenetic regulation by the menin pathway

2017 ◽  
Vol 24 (10) ◽  
pp. T147-T159 ◽  
Author(s):  
Zijie Feng ◽  
Jian Ma ◽  
Xianxin Hua
Keyword(s):  
Transcription Factors ◽  
Cell Signaling ◽  
Signaling Pathways ◽  
Gene Transcription ◽  
Epigenetic Regulation ◽  
Posttranslational Modifications ◽  
Genetic Model ◽  
Mirna Biogenesis ◽  
Endocrine Organs

There is a trend of increasing prevalence of neuroendocrine tumors (NETs), and the inherited multiple endocrine neoplasia type 1 (MEN1) syndrome serves as a genetic model to investigate how NETs develop and the underlying mechanisms. Menin, encoded by the MEN1 gene, at least partly acts as a scaffold protein by interacting with multiple partners to regulate cellular homeostasis of various endocrine organs. Menin has multiple functions including regulation of several important signaling pathways by controlling gene transcription. Here, we focus on reviewing the recent progress in elucidating the key biochemical role of menin in epigenetic regulation of gene transcription and cell signaling, as well as posttranslational regulation of menin itself. In particular, we will review the progress in studying structural and functional interactions of menin with various histone modifiers and transcription factors such as MLL, PRMT5, SUV39H1 and other transcription factors including c-Myb and JunD. Moreover, the role of menin in regulating cell signaling pathways such as TGF-beta, Wnt and Hedgehog, as well as miRNA biogenesis and processing will be described. Further, the regulation of the MEN1 gene transcription, posttranslational modifications and stability of menin protein will be reviewed. These various modes of regulation by menin as well as regulation of menin by various biological factors broaden the view regarding how menin controls various biological processes in neuroendocrine organ homeostasis.

scholarly journals Structural basis for PTPA interaction with the invariant C-terminal tail of PP2A

2014 ◽  
Vol 395 (7-8) ◽  
pp. 881-889 ◽  
Author(s):  
Christian Löw ◽  
Esben M. Quistgaard ◽  
Michael Kovermann ◽  
Madhanagopal Anandapadamanaban ◽  
Jochen Balbach ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Posttranslational Modifications ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Catalytic Subunit ◽  
Structural Basis ◽  
Interaction Site ◽  
Interaction Partners ◽  
Phosphatase 2A ◽  
Additional Interaction

Abstract Protein phosphatase 2A (PP2A) is a highly abundant heterotrimeric Ser/Thr phosphatase involved in the regulation of a variety of signaling pathways. The PP2A phosphatase activator (PTPA) is an ATP-dependent activation chaperone, which plays a key role in the biogenesis of active PP2A. The C-terminal tail of the catalytic subunit of PP2A is highly conserved and can undergo a number of posttranslational modifications that serve to regulate the function of PP2A. Here we have studied structurally the interaction of PTPA with the conserved C-terminal tail of the catalytic subunit carrying different posttranslational modifications. We have identified an additional interaction site for the invariant C-terminal tail of the catalytic subunit on PTPA, which can be modulated via posttranslational modifications. We show that phosphorylation of Tyr307PP2A-C or carboxymethylation of Leu309PP2A-C abrogates or diminishes binding of the C-terminal tail, whereas phosphorylation of Thr304PP2A-C is of no consequence. We suggest that the invariant C-terminal residues of the catalytic subunit can act as affinity enhancer for different PP2A interaction partners, including PTPA, and a different ‘code’ of posttranslational modifications can favour interactions to one subunit over others.

scholarly journals Proteomics in Neuropathic Pain Research

2008 ◽  
Vol 108 (2) ◽  
pp. 314-323 ◽  
Author(s):  
Ellen Niederberger ◽  
Gerd Geisslinger ◽  
David S. Warner ◽  
Mark A. Warner
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Signaling Pathways ◽  
Nerve Injury ◽  
Posttranslational Modifications ◽  
Molecular Mechanisms ◽  
Pharmacologic Treatment ◽  
Pain Research

Neuropathic pain is often caused by nerve injury or dysfunction in the peripheral and central nervous system and is frequently associated with allodynia and hyperalgesia. The underlying molecular mechanisms of neuropathic pain are largely unknown, and therefore, pharmacologic treatment is insufficient in many cases. To elucidate translational and posttranslational modifications in the nervous system that arise after nerve injury, a number of proteomic studies have been performed using different animal neuropathy models. The results of these proteomic approaches are summarized in this review to provide a better overview of proteins that are involved into the pathogenesis of nerve injury and neuropathic pain. This might allow a better understanding of the pathophysiologic signaling pathways in this impairment, facilitate the discovery of specific biomarkers, and thus promote the development of novel pain therapies.

Regulation of necroptosis signaling and cell death by reactive oxygen species

2016 ◽  
Vol 397 (7) ◽  
pp. 657-660 ◽  
Author(s):  
Simone Fulda
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Signaling Pathways ◽  
Posttranslational Modifications ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Alternative Form ◽  
Oxygen Species

Abstract Necroptosis has recently been identified as an alternative form of programmed cell death that is characterized by defined molecular mechanisms. Reactive oxygen species (ROS) are involved in the regulation of numerous signaling pathways, as they are highly reactive and can cause (ir)reversible posttranslational modifications. While the role of ROS in other modes of cell death has been extensively studied, its impact on necroptotic signaling and cell death is far less clear. The current minireview discusses the evidence for and against a role of ROS in necroptosis.

scholarly journals Organellophagy: Eliminating cellular building blocks via selective autophagy

2014 ◽  
Vol 205 (4) ◽  
pp. 435-445 ◽  
Author(s):  
Koji Okamoto
Keyword(s):  
Signaling Pathways ◽  
Posttranslational Modifications ◽  
Building Blocks ◽  
Eukaryotic Cells ◽  
Basic Principles ◽  
Selective Autophagy ◽  
Variable Environments ◽  
Selective Elimination ◽  
Key Steps ◽  
Related Proteins

Maintenance of organellar quality and quantity is critical for cellular homeostasis and adaptation to variable environments. Emerging evidence demonstrates that this kind of control is achieved by selective elimination of organelles via autophagy, termed organellophagy. Organellophagy consists of three key steps: induction, cargo tagging, and sequestration, which involve signaling pathways, organellar landmark molecules, and core autophagy-related proteins, respectively. In addition, posttranslational modifications such as phosphorylation and ubiquitination play important roles in recruiting and tailoring the autophagy machinery to each organelle. The basic principles underlying organellophagy are conserved from yeast to mammals, highlighting its biological relevance in eukaryotic cells.

scholarly journals The Pivotal Immunomodulatory and Anti-Inflammatory Effect of Histone-Lysine N-Methyltransferase in the Glioma Microenvironment: Its Biomarker and Therapy Potentials

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Seidu A. Richard ◽  
Kuugbee D. Eugene
Keyword(s):  
Stem Cells ◽  
Signaling Pathways ◽  
Posttranslational Modifications ◽  
Glioma Cells ◽  
Cell Types ◽  
Polycomb Group ◽  
Low Grade ◽  
Dynamic Component ◽  
Histone Lysine ◽  
Glioma Microenvironment

Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase that encrypts a member of the Polycomb group (PcG) family. EZH2 forms a repressive chromatin structure which eventually participates in regulating the development as well as lineage propagation of stem cells and glioma progression. Posttranslational modifications are distinct approaches for the adjusted modification of EZH2 in the development of cancer. The amino acid succession of EZH2 protein makes it appropriate for covalent modifications, like phosphorylation, acetylation, O-GlcNAcylation, methylation, ubiquitination, and sumoylation. The glioma microenvironment is a dynamic component that comprises, besides glioma cells and glioma stem cells, a complex network that comprises diverse cell types like endothelial cells, astrocytes, and microglia as well as stromal components, soluble factors, and the extracellular membrane. EZH2 is well recognized as an essential modulator of cell invasion as well as metastasis in glioma. EZH2 oversecretion was implicated in the malfunction of several fundamental signaling pathways like Wnt/β-catenin signaling, Ras and NF-κB signaling, PI3K/AKT signaling, β-adrenergic receptor signaling, and bone morphogenetic protein as well as NOTCH signaling pathways. EZH2 was more secreted in glioblastoma multiforme than in low-grade gliomas as well as extremely secreted in U251 and U87 human glioma cells. Thus, the blockade of EZH2 expression in glioma could be of therapeutic value for patients with glioma. The suppression of EZH2 gene secretion was capable of reversing temozolomide resistance in patients with glioma. EZH2 is a promising therapeutic as well as prognostic biomarker for the treatment of glioma.

scholarly journals Desmosomes as Signaling Hubs in the Regulation of Cell Behavior

2021 ◽  
Vol 9 ◽  
Author(s):  
Lisa Müller ◽  
Mechthild Hatzfeld ◽  
René Keil
Keyword(s):  
Signaling Pathways ◽  
Structural Properties ◽  
Posttranslational Modifications ◽  
Current Knowledge ◽  
Intercellular Junctions ◽  
Cell Behavior ◽  
Specific Expression ◽  
Tissue Integrity ◽  
Independent Functions ◽  
And Function

Desmosomes are intercellular junctions, which preserve tissue integrity during homeostatic and stress conditions. These functions rely on their unique structural properties, which enable them to respond to context-dependent signals and transmit them to change cell behavior. Desmosome composition and size vary depending on tissue specific expression and differentiation state. Their constituent proteins are highly regulated by posttranslational modifications that control their function in the desmosome itself and in addition regulate a multitude of desmosome-independent functions. This review will summarize our current knowledge how signaling pathways that control epithelial shape, polarity and function regulate desmosomes and how desmosomal proteins transduce these signals to modulate cell behavior.

Neurofilaments and Paired Helical Filaments

1985 ◽  
Vol 43 ◽  
pp. 740-743
Author(s):  
J. Metuzals
Keyword(s):  
Animal Model ◽  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Giant Axon ◽  
Paired Helical Filaments ◽  
Squid Giant Axon ◽  
In Vitro Experiments ◽  
Thin Sections ◽  
Structural Relationships

It has been demonstrated that the neurofibrillary tangles in biopsies of Alzheimer patients, composed of typical paired helical filaments (PHF), consist also of typical neurofilaments (NF) and 15nm wide filaments. Close structural relationships, and even continuity between NF and PHF, have been observed. In this paper, such relationships are investigated from the standpoint that the PHF are formed through posttranslational modifications of NF. To investigate the validity of the posttranslational modification hypothesis of PHF formation, we have identified in thin sections from frontal lobe biopsies of Alzheimer patients all existing conformations of NF and PHF and ordered these conformations in a hypothetical sequence. However, only experiments with animal model preparations will prove or disprove the validity of the interpretations of static structural observations made on patients. For this purpose, the results of in vitro experiments with the squid giant axon preparations are compared with those obtained from human patients. This approach is essential in discovering etiological factors of Alzheimer's disease and its early diagnosis.

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