scholarly journals Charting the N-Terminal Acetylome: A Comprehensive Map of Human NatA Substrates

2021 ◽  
Vol 22 (19) ◽  
pp. 10692
Author(s):  
Petra Van Damme
Keyword(s):  
Steady State ◽  
Enzymatic Activity ◽  
Protein Stability ◽  
Ribosomal Proteins ◽  
Fold Increase ◽  
Regulatory Subunit ◽  
Preinitiation Complex ◽  
Eukaryotic Protein ◽  
Steady State Levels ◽  
High Enzymatic Activity

N-terminal acetylation (Nt-acetylation) catalyzed by conserved N-terminal acetyltransferases or NATs embodies a modification with one of the highest stoichiometries reported for eukaryotic protein modifications to date. Comprising the catalytic N-alpha acetyltransferase (NAA) subunit NAA10 plus the ribosome anchoring regulatory subunit NAA15, NatA represents the major acetyltransferase complex with up to 50% of all mammalian proteins representing potential substrates. Largely in consequence of the essential nature of NatA and its high enzymatic activity, its experimentally confirmed mammalian substrate repertoire remained poorly charted. In this study, human NatA knockdown conditions achieving near complete depletion of NAA10 and NAA15 expression resulted in lowered Nt-acetylation of over 25% out of all putative NatA targets identified, representing an up to 10-fold increase in the reported number of substrate N-termini affected upon human NatA perturbation. Besides pointing to less efficient NatA substrates being prime targets, several putative NatE substrates were shown to be affected upon human NatA knockdown. Intriguingly, next to a lowered expression of ribosomal proteins and proteins constituting the eukaryotic 48S preinitiation complex, steady-state levels of protein N-termini additionally point to NatA Nt-acetylation deficiency directly impacting protein stability of knockdown affected targets.

cAMP, myosin dephosphorylation, and isometric relaxation of airway smooth muscle

1988 ◽  
Vol 64 (2) ◽  
pp. 705-709 ◽  
Author(s):  
P. de Lanerolle
Keyword(s):  
Smooth Muscle ◽  
Steady State ◽  
Muscle Relaxation ◽  
Fold Increase ◽  
Treatment Results ◽  
Myosin Phosphorylation ◽  
Temporal Relationships ◽  
Steady State Levels ◽  
Two Parameters ◽  
Camp Levels

The temporal relationships among increases in adenosine 3',5'-cyclic monophosphate (cAMP) levels, myosin dephosphorylation, and relaxation were investigated to clarify the mechanisms of airway muscle relaxation. Canine tracheal muscles isometrically contracted (82% of maximum force) with 10(-6) M methacholine were relaxed by adding either 4 x 10(-7) M atropine or 4 x 10(-5) M forskolin. Atropine had no effect on cAMP levels; myosin phosphorylation and force, however, decayed at the same rates and these two parameters returned to their basal pre-methacholine levels within 5 min. Forskolin treatment results in about a 10-fold increase in cAMP levels; myosin phosphorylation and force decayed simultaneously to their respective steady-state levels by 10 min but neither parameter returned to its pre-methacholine level. The addition of forskolin to muscles maximally contracted with 10(-4) M methacholine leads to about a 30-fold increase in cAMP levels. However, there are minimal decreases in myosin phosphorylation and force in these muscles. Thus myosin dephosphorylation appears to be essential for airway muscle relaxation, whereas an increase in cAMP in the absence of myosin dephosphorylation is insufficient to cause relaxation. Moreover, myosin dephosphorylation appears to be a common step in the cAMP-independent and cAMP-dependent mechanisms for airway muscle relaxation.

scholarly journals Regulation of intracellular cyclic GMP concentration by light and calcium in electropermeabilized rod photoreceptors.

1994 ◽  
Vol 103 (1) ◽  
pp. 67-86 ◽  
Author(s):  
V J Coccia ◽  
R H Cote
Keyword(s):  
Steady State ◽  
Guanylate Cyclase ◽  
Time Course ◽  
Calcium Concentration ◽  
Fold Increase ◽  
Photoreceptor Cells ◽  
Cyclase Activity ◽  
Free Calcium ◽  
Guanylate Cyclase Activity ◽  
Steady State Levels

This study examines the regulation of cGMP by illumination and by calcium during signal transduction in vertebrate retinal photoreceptor cells. We employed an electropermeabilized rod outer segment (EP-ROS) preparation which permits perfusion of low molecular weight compounds into the cytosol while retaining many of the features of physiologically competent, intact rod outer segments (ROS). When nucleotide-depleted EP-ROS were incubated with MgGTP, time- and dose-dependent increases in intracellular cGMP levels were observed. The steady state cGMP concentration in EP-ROS (0.007 mol cGMP per mol rhodopsin) approached the cGMP concentration in intact ROS. Flash illumination of EP-ROS in a 250-nM free calcium medium resulted in a transient decrease in cGMP levels; this occurred in the absence of changes in calcium concentration. The kinetics of the cGMP response to flash illumination of EP-ROS were similar to that of intact ROS. To further examine the effects of calcium on cGMP metabolism, dark-adapted EP-ROS were incubated with MgGTP containing various concentrations of calcium. We observed a twofold increase in cGMP steady state levels as the free calcium was lowered from 1 microM to 20 nM; this increase was comparable to the behavior of intact ROS. Measurements of guanylate cyclase activity in EP-ROS showed a 3.5-fold increase in activity over this range of calcium concentrations, indicating a retention of calcium regulation of guanylate cyclase in EP-ROS preparations. Flash illumination of EP-ROS in either a 50- or 250-nM free calcium medium revealed a slowing of the recovery time course at the lower calcium concentration. This observation conflicts with any hypothesis whereby a reduction in free calcium concentration hastens the recovery of cytoplasmic cGMP levels, either by stimulating guanylate cyclase activity or by inhibiting phosphodiesterase activity. We conclude that changes in the intracellular calcium concentration during visual transduction may have more complex effects on the recovery of the photoresponse than can be accounted for solely by guanylate cyclase activation.

Expression of type I and III collagen genes during differentiation of embryonic chicken myoblasts in culture

1984 ◽  
Vol 4 (8) ◽  
pp. 1483-1492
Author(s):  
L C Gerstenfeld ◽  
D R Crawford ◽  
H Boedtker ◽  
P Doty
Keyword(s):  
Steady State ◽  
Cell Cultures ◽  
Sodium Dodecyl ◽  
Fold Increase ◽  
Myoblast Differentiation ◽  
Type I ◽  
Mrna Levels ◽  
Embryonic Chicken ◽  
Steady State Levels ◽  
Alpha Actin

Expression of type I and III procollagen genes was studied in embryonic chicken myoblast cell cultures, obtained from thigh muscles of 11-day-old embryos. Differentiation initiated by the addition of ovotransferrin (30 micrograms/ml) was followed visually by phase-contrast microscopy. Myoblast fusion and myotube formation were detected by day 3 and appeared to be complete by day 7. The synthesis of procollagens was monitored by labeling cell cultures for 1 h with [3H]proline and determining the radioactivity in procollagen chains by scanning densitometry of the fluorograms of the sodium dodecyl sulfate-polyacrylamide gels. A 10- to 20-fold increase in the rate of pro alpha-1(I), pro alpha-2(I), and pro alpha-1(III) collagen synthesis was observed, with the greatest increase occurring between days 3 and 9. Collagen mRNA levels in the myoblast cultures were examined by Northern blot and dot blot hybridization assays. The 10- to 20-fold increased rate of protein synthesis was accompanied by a 15-fold increase in the steady-state levels of pro alpha-1(I) and pro alpha-2(I) mRNAs and a 10-fold increase in the steady-state levels of pro alpha-1(III). As a correlate to the studies of collagen expression during myoblast differentiation, the expression of actin mRNAs was examined. Although alpha actin could be detected by day 4, a complete switch from lambda and beta to alpha actin was not observed in the time periods examined. Similar results were obtained in the analysis of RNA extracted from embryonic legs at days 12 and 17 of gestation. Myoblast differentiation is manifested by the accumulation of both muscle-specific mRNAs, such as actin, and type I and III procollagen mRNAs.

scholarly journals Expression of type I and III collagen genes during differentiation of embryonic chicken myoblasts in culture.

1984 ◽  
Vol 4 (8) ◽  
pp. 1483-1492 ◽  
Author(s):  
L C Gerstenfeld ◽  
D R Crawford ◽  
H Boedtker ◽  
P Doty
Keyword(s):  
Steady State ◽  
Cell Cultures ◽  
Sodium Dodecyl ◽  
Fold Increase ◽  
Myoblast Differentiation ◽  
Type I ◽  
Mrna Levels ◽  
Embryonic Chicken ◽  
Steady State Levels ◽  
Alpha Actin

Expression of type I and III procollagen genes was studied in embryonic chicken myoblast cell cultures, obtained from thigh muscles of 11-day-old embryos. Differentiation initiated by the addition of ovotransferrin (30 micrograms/ml) was followed visually by phase-contrast microscopy. Myoblast fusion and myotube formation were detected by day 3 and appeared to be complete by day 7. The synthesis of procollagens was monitored by labeling cell cultures for 1 h with [3H]proline and determining the radioactivity in procollagen chains by scanning densitometry of the fluorograms of the sodium dodecyl sulfate-polyacrylamide gels. A 10- to 20-fold increase in the rate of pro alpha-1(I), pro alpha-2(I), and pro alpha-1(III) collagen synthesis was observed, with the greatest increase occurring between days 3 and 9. Collagen mRNA levels in the myoblast cultures were examined by Northern blot and dot blot hybridization assays. The 10- to 20-fold increased rate of protein synthesis was accompanied by a 15-fold increase in the steady-state levels of pro alpha-1(I) and pro alpha-2(I) mRNAs and a 10-fold increase in the steady-state levels of pro alpha-1(III). As a correlate to the studies of collagen expression during myoblast differentiation, the expression of actin mRNAs was examined. Although alpha actin could be detected by day 4, a complete switch from lambda and beta to alpha actin was not observed in the time periods examined. Similar results were obtained in the analysis of RNA extracted from embryonic legs at days 12 and 17 of gestation. Myoblast differentiation is manifested by the accumulation of both muscle-specific mRNAs, such as actin, and type I and III procollagen mRNAs.

scholarly journals The critical role of T cells in glucocorticoid-induced osteoporosis

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Lin Song ◽  
Lijuan Cao ◽  
Rui Liu ◽  
Hui Ma ◽  
Yanan Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Steady State ◽  
Side Effects ◽  
Critical Role ◽  
Wild Type ◽  
Receptor Activator ◽  
Steady State Levels ◽  
Induced Apoptosis

AbstractGlucocorticoids (GC) are widely used clinically, despite the presence of significant side effects, including glucocorticoid-induced osteoporosis (GIOP). While GC are believed to act directly on osteoblasts and osteoclasts to promote osteoporosis, the detailed underlying molecular mechanism of GC-induced osteoporosis is still not fully elucidated. Here, we show that lymphocytes play a pivotal role in regulating GC-induced osteoporosis. We show that GIOP could not be induced in SCID mice that lack T cells, but it could be re-established by adoptive transfer of splenic T cells from wild-type mice. As expected, T cells in the periphery are greatly reduced by GC; instead, they accumulate in the bone marrow where they are protected from GC-induced apoptosis. These bone marrow T cells in GC-treated mice express high steady-state levels of NF-κB receptor activator ligand (RANKL), which promotes the formation and maturation of osteoclasts and induces osteoporosis. Taken together, these findings reveal a critical role for T cells in GIOP.

The Olympic Games as a News Shock

2017 ◽  
Vol 19 (6) ◽  
pp. 884-906 ◽  
Author(s):  
Viktoria C. E. Langer ◽  
Wolfgang Maennig ◽  
Felix Richter
Keyword(s):  
Steady State ◽  
Olympic Games ◽  
Structural Models ◽  
Adjustment Process ◽  
Dynamic Adjustment ◽  
Economic Variables ◽  
Long Run ◽  
News Shock ◽  
Steady State Levels ◽  
The Olympic Games

The awarding of the Olympic Games to a certain city or the announcement of a city’s Olympic bid may be considered as a news shock that affects agents’ market expectations. A news shock implies potential impacts on the dynamic adjustment process that change not only the volatility but also the long-run steady-state levels of endogenous economic variables. In this study, we contribute to and extend previous researchers’ attempts to empirically test for the Olympic Games as a news shock by implementing full structural models and by matching Olympic hosts and bidders to structurally similar countries.

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