The intricate dance of post-translational modifications in the rhythm of life

Hirano, Arisa; Fu, Ying‐Hui; Ptáček, Louis J.

doi:10.1038/nsmb.3326

Cited by 153 publications

(145 citation statements)

References 120 publications

Supporting

Mentioning

141

Contrasting

Unclassified

Order By: Relevance

“…Sumoylation (Cardone et al, 2005), acetylation (Doi et al, 2006; Hirayama et al, 2007; Asher et al, 2008), dephosphorylation (Reischl and Kramer, 2011), and ubiquitination (DeBruyne et al, 2015) further post-translationally regulate the clock proteins (Hirano et al, 2016). Furthermore, epigenetic regulation has been found to play a role in clock regulation (Papazyan et al, 2016) and rhythmic changes in the chromatin landscape of the DNA (Koike et al, 2012) and histone and DNA modifications have been reported (Ripperger and Merrow, 2011; Sahar and Sassone-Corsi, 2013; Azzi et al, 2014), and so have splicing and RNA modification as well as ribosomal translation (McGlincy et al, 2012; Lim and Allada, 2013; Perez-Santangelo et al, 2014; Jang et al, 2015; Janich et al, 2015).…”

Section: The Circadian Timing System and Its Multilevel Intersubjmentioning

confidence: 99%

Systems Chronotherapeutics

et al. 2017

View full text Add to dashboard Cite

Chronotherapeutics aim at treating illnesses according to the endogenous biologic rhythms, which moderate xenobiotic metabolism and cellular drug response. The molecular clocks present in individual cells involve approximately fifteen clock genes interconnected in regulatory feedback loops. They are coordinated by the suprachiasmatic nuclei, a hypothalamic pacemaker, which also adjusts the circadian rhythms to environmental cycles. As a result, many mechanisms of diseases and drug effects are controlled by the circadian timing system. Thus, the tolerability of nearly 500 medications varies by up to fivefold according to circadian scheduling, both in experimental models and/or patients. Moreover, treatment itself disrupted, maintained, or improved the circadian timing system as a function of drug timing. Improved patient outcomes on circadian-based treatments (chronotherapy) have been demonstrated in randomized clinical trials, especially for cancer and inflammatory diseases. However, recent technological advances have highlighted large interpatient differences in circadian functions resulting in significant variability in chronotherapy response. Such findings advocate for the advancement of personalized chronotherapeutics through interdisciplinary systems approaches. Thus, the combination of mathematical, statistical, technological, experimental, and clinical expertise is now shaping the development of dedicated devices and diagnostic and delivery algorithms enabling treatment individualization. In particular, multiscale systems chronopharmacology approaches currently combine mathematical modeling based on cellular and whole-body physiology to preclinical and clinical investigations toward the design of patient-tailored chronotherapies. We review recent systems research works aiming to the individualization of disease treatment, with emphasis on both cancer management and circadian timing system–resetting strategies for improving chronic disease control and patient outcomes.

show abstract

Section: The Circadian Timing System and Its Multilevel Intersubjmentioning

confidence: 99%

Systems Chronotherapeutics

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The circadian clock is also targeted by multiple posttranslational modifications that increase the robustness of the oscillatory system by fine-tuning the localization and degradation of core oscillator proteins (2). Notably, proteasome-mediated degradation of core circadian proteins is necessary for the rhythmic expression of core clock genes (19).…”

Section: The Molecular Circadian Clockmentioning

confidence: 99%

“…In response to daily changes in nutrient availability and physiological states, numerous posttranslational modifications of the circadian clock have been identified, and modifications such as phosphorylation, ubiquitination, acetylation, O-GlcNacylation, and SUMOylation were shown to have a direct role in fine-tuning the timing of the molecular circadian clock and related metabolic pathways [for reviews, see Ref. (2, 133)].…”

Section: Characterization Of the Circadian Proteomes And Posttranslatmentioning

confidence: 99%

“…This synchronizes subsidiary peripheral oscillators present in nearly every cell of the body (1). At the molecular level, circadian rhythms in gene expression are generated by interconnected transcriptional and translational feedback loops (TTFLs), in which multiple layers of control, including temporal transcriptional, posttranscriptional, and posttranslational regulation, play important roles (2, 3). …”

mentioning

confidence: 99%

See 1 more Smart Citation

Regulation of Mammalian Physiology by Interconnected Circadian and Feeding Rhythms

et al. 2017

View full text Add to dashboard Cite

Circadian clocks are endogenous timekeeping systems that adapt in an anticipatory fashion the physiology and behavior of most living organisms. In mammals, the master pacemaker resides in the suprachiasmatic nucleus and entrains peripheral clocks using a wide range of signals that differentially schedule physiology and gene expression in a tissue-specific manner. The peripheral clocks, such as those found in the liver, are particularly sensitive to rhythmic external cues like feeding behavior, which modulate the phase and amplitude of rhythmic gene expression. Consequently, the liver clock temporally tunes the expression of many genes involved in metabolism and physiology. However, the circadian modulation of cellular functions also relies on multiple layers of posttranscriptional and posttranslational regulation. Strikingly, these additional regulatory events may happen independently of any transcriptional oscillations, showing that complex regulatory networks ultimately drive circadian output functions. These rhythmic events also integrate feeding-related cues and adapt various metabolic processes to food availability schedules. The importance of such temporal regulation of metabolism is illustrated by metabolic dysfunctions and diseases resulting from circadian clock disruption or inappropriate feeding patterns. Therefore, the study of circadian clocks and rhythmic feeding behavior should be of interest to further advance our understanding of the prevention and therapy of metabolic diseases.

show abstract

“…There is a pressing, unmet need for a polysaccharide sequence mapping tool, since these polymers lack a canonical sequence and instead the pattern of monomer and branching sequence depends on several factors, determined by cellular metabolism, developmental stage, nutrient availability and others. 1 Even in polymers with canonical sequences, such as proteins and nucleic acids, posttranslational modification of proteins by glycosylation, phosphorylation and other additions, 2,3 as well as epigenetic modifications of nucleic acids, 4 occur in micro-and macroheterogeneous patterns that are not always easy to discern. Recently, the emergence of sequence-defined synthetic polymers has created a new class of materials in which relevant properties may be controlled with much greater precision than before, where sequence directly controls function.…”

Section: Introductionmentioning

confidence: 99%

Polymer sequencing by molecular machines: a framework for predicting the resolving power of a sliding contact force spectroscopy sequencing method

et al. 2017

View full text Add to dashboard Cite

We evaluate an AFM-based single molecule force spectroscopy method for mapping sequences in otherwise difficult to sequence heteropolymers, including glycosylated proteins and glycans. The sliding contact force spectroscopy (SCFS) method exploits a sliding contact made between a nanopore threaded over a polymer axle and an AFM probe. We find that for sliding α-and β-cyclodextrin nanopores over a wide range of hydrophilic monomers, the free energy of sliding is proportional to the sum of two dimensionless, easily calculable parameters representing the relative partitioning of the monomer inside the nanopore or in the aqueous phase, and the friction arising from sliding the nanopore over the monomer.Using this relationship we calculate sliding energies for nucleic acids, amino acids, glycan and synthetic monomers and predict on the basis of these calculations that SCFS will detect N-and O-glycosylation of proteins and patterns of sidechains in glycans. For these applications, SCFS offers an alternative to sequence mapping by mass spectrometry or newly-emerging nanopore technologies that may be easily implemented using a standard AFM.

show abstract

The intricate dance of post-translational modifications in the rhythm of life

Cited by 153 publications

References 120 publications

Systems Chronotherapeutics

Systems Chronotherapeutics

Regulation of Mammalian Physiology by Interconnected Circadian and Feeding Rhythms

Polymer sequencing by molecular machines: a framework for predicting the resolving power of a sliding contact force spectroscopy sequencing method

Contact Info

Product

Resources

About