Biological Consequences of Priming Phosphorylation in Cancer Development

Aoki, Katsuhiko; Yoshida, Kiyotsugu

doi:10.5772/intechopen.70039

Cited by 5 publications

(5 citation statements)

References 147 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A subset of degrons are regulated by phosphorylation and thus are called phosphodegrons ( 232 , 233 ). Phosphodegrons are short linear amino acid sequences, D/E-S/T- G XX-S/T-P or LL -S/T- P XX-S/T-P, where the phosphorylation of S/T residues promotes protein clearance through stimulation of subsequent ubiquitination and proteasomal degradation ( 232 , 233 ). Proteins can also contain other motifs that promote degradation by the autophagy-lysosomes system.…”

Section: Effect Of Ptms On Tau Degradationmentioning

confidence: 99%

See 1 more Smart Citation

Tau Post-translational Modifications: Dynamic Transformers of Tau Function, Degradation, and Aggregation

2021

View full text Add to dashboard Cite

Post-translational modifications (PTMs) on tau have long been recognized as affecting protein function and contributing to neurodegeneration. The explosion of information on potential and observed PTMs on tau provides an opportunity to better understand these modifications in the context of tau homeostasis, which becomes perturbed with aging and disease. Prevailing views regard tau as a protein that undergoes abnormal phosphorylation prior to its accumulation into the toxic aggregates implicated in Alzheimer's disease (AD) and other tauopathies. However, the phosphorylation of tau may, in fact, represent part of the normal but interrupted function and catabolism of the protein. In addition to phosphorylation, tau undergoes another forms of post-translational modification including (but not limited to), acetylation, ubiquitination, glycation, glycosylation, SUMOylation, methylation, oxidation, and nitration. A holistic appreciation of how these PTMs regulate tau during health and are potentially hijacked in disease remains elusive. Recent studies have reinforced the idea that PTMs play a critical role in tau localization, protein-protein interactions, maintenance of levels, and modifying aggregate structure. These studies also provide tantalizing clues into the possibility that neurons actively choose how tau is post-translationally modified, in potentially competitive and combinatorial ways, to achieve broad, cellular programs commensurate with the distinctive environmental conditions found during development, aging, stress, and disease. Here, we review tau PTMs and describe what is currently known about their functional impacts. In addition, we classify these PTMs from the perspectives of protein localization, electrostatics, and stability, which all contribute to normal tau function and homeostasis. Finally, we assess the potential impact of tau PTMs on tau solubility and aggregation. Tau occupies an undoubtedly important position in the biology of neurodegenerative diseases. This review aims to provide an integrated perspective of how post-translational modifications actively, purposefully, and dynamically remodel tau function, clearance, and aggregation. In doing so, we hope to enable a more comprehensive understanding of tau PTMs that will positively impact future studies.

show abstract

Section: Effect Of Ptms On Tau Degradationmentioning

confidence: 99%

“…where the phosphorylation of S/T residues promotes protein clearance through stimulation of subsequent ubiquitination and proteasomal degradation (232,233). Proteins can also contain other motifs that promote degradation by the autophagy-lysosomes system.…”

Section: Phosphodegrons Are Short Linear Amino Acid Sequences D/e-mentioning

confidence: 99%

Tau Post-translational Modifications: Dynamic Transformers of Tau Function, Degradation, and Aggregation

2021

View full text Add to dashboard Cite

show abstract

“…CK1s are involved in various cellular processes, such as in Wnt and Hedgehog signalling, circadian rhythm, nucleo-cytoplasmic shuttling, DNA repair, DNA transcription and others [ 138 , 139 , 140 ]. CK1s are known to have a wide range of substrates [ 138 ], while they are involved in hierarchical phosphorylation events, acting either as a priming or as a processive kinase [ 141 , 142 ]. Thus, deregulation of CK1 isoforms is implicated in several diseases, such as neurodegenerative, sleeping disorders, and neoplasia [ 137 ].…”

Section: Casein Kinasesmentioning

confidence: 99%

Leishmania Protein Kinases: Important Regulators of the Parasite Life Cycle and Molecular Targets for Treating Leishmaniasis

Efstathiou

Smirlis

2021

Microorganisms

View full text Add to dashboard Cite

Leishmania is a protozoan parasite of the trypanosomatid family, causing a wide range of diseases with different clinical manifestations including cutaneous, mucocutaneous and visceral leishmaniasis. According to WHO, one billion people are at risk of Leishmania infection as they live in endemic areas while there are 12 million infected people worldwide. Annually, 0.9–1.6 million new infections are reported and 20–50 thousand deaths occur due to Leishmania infection. As current chemotherapy for treating leishmaniasis exhibits numerous drawbacks and due to the lack of effective human vaccine, there is an urgent need to develop new antileishmanial therapy treatment. To this end, eukaryotic protein kinases can be ideal target candidates for rational drug design against leishmaniasis. Eukaryotic protein kinases mediate signal transduction through protein phosphorylation and their inhibition is anticipated to be disease modifying as they regulate all essential processes for Leishmania viability and completion of the parasitic life cycle including cell-cycle progression, differentiation and virulence. This review highlights existing knowledge concerning the exploitation of Leishmania protein kinases as molecular targets to treat leishmaniasis and the current knowledge of their role in the biology of Leishmania spp. and in the regulation of signalling events that promote parasite survival in the insect vector or the mammalian host.

show abstract

“…In addition to time and space, there are many other elements that are simplified or disregarded when scaling up models of signaling. Examples include protein complex formation or priming phosphorylation events, both of which are required for certain signaling events to take place (Aoki & Yoshida, 2017 ). Moreover, when multiple interactions influence a single downstream protein, determining its signaling activity is not always possible from a simple graphical description (activity flow).…”

Section: Introductionmentioning

confidence: 99%

Integrating knowledge and omics to decipher mechanisms via large‐scale models of signaling networks

Garrido‐Rodríguez

Zirngibl

Ivanova

et al. 2022

Molecular Systems Biology

View full text Add to dashboard Cite

Signal transduction governs cellular behavior, and its dysregulation often leads to human disease. To understand this process, we can use network models based on prior knowledge, where nodes represent biomolecules, usually proteins, and edges indicate interactions between them. Several computational methods combine untargeted omics data with prior knowledge to estimate the state of signaling networks in specific biological scenarios. Here, we review, compare, and classify recent network approaches according to their characteristics in terms of input omics data, prior knowledge and underlying methodologies. We highlight existing challenges in the field, such as the general lack of ground truth and the limitations of prior knowledge. We also point out new omics developments that may have a profound impact, such as single-cell proteomics or large-scale profiling of protein conformational changes. We provide both an introduction for interested users seeking strategies to study cell signaling on a large scale and an update for seasoned modelers.

show abstract

Biological Consequences of Priming Phosphorylation in Cancer Development

Cited by 5 publications

References 147 publications

Tau Post-translational Modifications: Dynamic Transformers of Tau Function, Degradation, and Aggregation

Tau Post-translational Modifications: Dynamic Transformers of Tau Function, Degradation, and Aggregation

Leishmania Protein Kinases: Important Regulators of the Parasite Life Cycle and Molecular Targets for Treating Leishmaniasis

Integrating knowledge and omics to decipher mechanisms via large‐scale models of signaling networks

Contact Info

Product

Resources

About