scholarly journals Universality and non-universality of the growth law

2021 ◽  
Author(s):  
Qirun Wang ◽  
Jie Lin
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Ribosomal Proteins ◽  
Correlation Coefficients ◽  
Growth Conditions ◽  
Proliferating Cells ◽  
Translation Speed ◽  
Nutrient Quality ◽  
Degradation Rates ◽  
Mass Fractions

An approximately linear relationship between the fraction of ribosomal proteins in the proteome (ϕR) and the growth rate (μ) holds in proliferating cells when the nutrient quality changes, often referred to as a growth law. While a simple model assuming a constant translation speed of ribosomes without protein degradation can rationalize this growth law, real protein synthesis processes are more complex. This work proposes a general theoretical framework of protein synthesis, taking account of heterogeneous translation speeds among proteins and finite protein degradation. We introduce ribosome allocations as the fraction of active ribosomes producing certain proteins, with two correlation coefficients respectively quantifying the correlation between translation speeds and ribosome allocations, and between protein degradation rates and mass fractions. We prove that the growth law curve generally follows ϕR = (μ + c1)/(c2μ + c3) where c1, c2, and c3 are constants depending on the above correlation coefficients and the translation speed of ribosomal proteins. Our theoretical predictions of ϕR agree with existing data of Saccharomyces cerevisiae. We demonstrate that when different environments share similar correlation coefficients, the growth law curve is universal and up-bent relative to a linear line in slow-growth conditions, which appears valid for Escherichia coli. However, the growth law curve is non-universal and environmental-specific when the environments have significantly different correlation coefficients. Our theories allow us to estimate the translation speeds of ribosomal and non-ribosomal proteins based on the experimental growth law curves.

Regulation of Ribosomal Protein mRNA Content and Translation in Growth-Stimulated Mouse Fibroblasts

1982 ◽  
Vol 2 (6) ◽  
pp. 685-693
Author(s):  
Pamela K. Geyer ◽  
Oded Meyuhas ◽  
Robert P. Perry ◽  
Lee F. Johnson
Keyword(s):  
Protein Synthesis ◽  
Ribosomal Protein ◽  
Ribosomal Proteins ◽  
Growth Stimulation ◽  
Growth Conditions ◽  
Resting Cells ◽  
Serum Stimulation ◽  
Mrna Content ◽  
Ribosomal Protein Synthesis ◽  
Polyadenylated Mrna

When resting (G 0 ) mouse 3T6 fibroblasts are serum stimulated to reenter the cell cycle, the rates of synthesis of rRNA and ribosomal proteins increase, resulting in an increase in ribosome content beginning about 6 h after stimulation. In this study, we monitored the content, metabolism, and translation of ribosomal protein mRNA (rp mRNA) in resting, exponentially growing, and serum-stimulated 3T6 cells. Cloned cDNAs for seven rp mRNAs were used in DNA-excess filter hybridization studies to assay rp mRNA. We found that about 85% of rp mRNA is polyadenylated under all growth conditions. The rate of labeling of rp mRNA relative to total polyadenylated mRNA changed very little after stimulation. The half-life of rp mRNA was about 11 h in resting cells and about 8 h in exponentially growing cells, values which are similar to the half-lives of total mRNA in resting and growing cells (about 9 h). The content of rp mRNA relative to total mRNA was about the same in resting and growing 3T6 cells. Furthermore, the total amount of rp mRNA did not begin to increase until about 6 h after stimulation. Since an increase in rp mRNA content did not appear to be responsible for the increase in ribosomal protein synthesis, we determined the efficiency of translation of rp mRNA under different conditions. We found that about 85% of pulse-labeled rp mRNA was associated with polysomes in exponentially growing cells. In resting cells, however, only about half was associated with polysomes, and about 30% was found in the monosomal fraction. The distribution shifted to that found in growing cells within 3 h after serum stimulation. Similar results were obtained when cells were labeled for 10.5 h. About 70% of total polyadenylated mRNA was in the polysome fraction in all growth states regardless of labeling time, indicating that the shift in mRNA distribution was species specific. These results indicate that the content and metabolism of rp mRNA do not change significantly after growth stimulation. The rate of ribosomal protein synthesis appears to be controlled during the resting-growing transition by an alteration of the efficiency of translation of rp mRNA, possibly at the level of protein synthesis initiation.

scholarly journals The effect of insulin and intermittent mechanical stretching on rates of protein synthesis and degradation in isolated rabbit muscle

1985 ◽  
Vol 230 (1) ◽  
pp. 117-123 ◽  
Author(s):  
R M Palmer ◽  
P A Bain ◽  
P J Reeds
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Suppressive Effect ◽  
Rabbit Muscle ◽  
Degradation Rates ◽  
Forelimb Muscles ◽  
Amino Acid Balance ◽  
Mechanical Stretching ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Tyrosine balance and protein synthesis were studied during the same incubation in isolated rabbit forelimb muscles. From these measurements, protein degradation was calculated. Isolated muscles were usually in a state of negative amino acid balance, principally as a result of the 75% decrease in protein synthesis. Muscles from rabbits starved for 18 h had lower rates of both protein synthesis and degradation compared with muscles from normally fed rabbits. Intermittent mechanical stretching and the addition of insulin at 100 microunits/ml increased rates of both protein synthesis and degradation. Increases in the rate of protein synthesis were proportionately greater in the muscles from starved animals. In muscles from both fed and starved donors, increases in protein-synthesis rates owing to intermittent stretching and insulin were proportionately greater than the increases in degradation rates. For example, insulin increased the rate of protein synthesis in the muscles from starved donors by 111% and the rate of degradation by 31%. Insulin also increased the rate of protein synthesis when added at a higher concentration (100 munits/ml); at this concentration, however, the rate of protein degradation was not increased. The suppressive effect of insulin on high rates of protein degradation in other skeletal-muscle preparations may reflect a non-physiological action of the hormone.

scholarly journals Effect of hypophysectomy on the rates of protein synthesis and degradation in rat liver

1979 ◽  
Vol 178 (3) ◽  
pp. 725-731 ◽  
Author(s):  
R D Conde
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Rat Liver ◽  
Protein Metabolism ◽  
Plasma Proteins ◽  
Degradation Rates ◽  
Hypophysectomized Rats ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

The effect of hypophysectomy on the protein metabolism of the liver in vivo was studied. Fractional rates of protein synthesis and degradation were determined in the livers of normal and hypophysectomized rats. Synthesis was measured after the injection of massive amounts of radioactive leucine. Degradation was estimated either as the balance between synthesis and accumulation of stable liver proteins or from the disappearance of radioactivity from the proteins previously labelled by the injection of NaH14CO3. The results indicate that: (1) hypophysectomy diminishes the capacity of the liver to synthesize proteins in vivo, mainly of those that are exported as plasma proteins; (2) livers of both normal and hypophysectomized rats show identical protein-degradation rates, whereas plasma proteins are degraded slowly after hypophysectomy.

scholarly journals Regulation of Ribosomal Protein mRNA Content and Translation in Growth-Stimulated Mouse Fibroblasts

1982 ◽  
Vol 2 (6) ◽  
pp. 685-693 ◽  
Author(s):  
Pamela K. Geyer ◽  
Oded Meyuhas ◽  
Robert P. Perry ◽  
Lee F. Johnson
Keyword(s):  
Protein Synthesis ◽  
Ribosomal Protein ◽  
Ribosomal Proteins ◽  
Growth Stimulation ◽  
Growth Conditions ◽  
Resting Cells ◽  
Serum Stimulation ◽  
Mrna Content ◽  
Ribosomal Protein Synthesis ◽  
Polyadenylated Mrna

When resting (G0) mouse 3T6 fibroblasts are serum stimulated to reenter the cell cycle, the rates of synthesis of rRNA and ribosomal proteins increase, resulting in an increase in ribosome content beginning about 6 h after stimulation. In this study, we monitored the content, metabolism, and translation of ribosomal protein mRNA (rp mRNA) in resting, exponentially growing, and serum-stimulated 3T6 cells. Cloned cDNAs for seven rp mRNAs were used in DNA-excess filter hybridization studies to assay rp mRNA. We found that about 85% of rp mRNA is polyadenylated under all growth conditions. The rate of labeling of rp mRNA relative to total polyadenylated mRNA changed very little after stimulation. The half-life of rp mRNA was about 11 h in resting cells and about 8 h in exponentially growing cells, values which are similar to the half-lives of total mRNA in resting and growing cells (about 9 h). The content of rp mRNA relative to total mRNA was about the same in resting and growing 3T6 cells. Furthermore, the total amount of rp mRNA did not begin to increase until about 6 h after stimulation. Since an increase in rp mRNA content did not appear to be responsible for the increase in ribosomal protein synthesis, we determined the efficiency of translation of rp mRNA under different conditions. We found that about 85% of pulse-labeled rp mRNA was associated with polysomes in exponentially growing cells. In resting cells, however, only about half was associated with polysomes, and about 30% was found in the monosomal fraction. The distribution shifted to that found in growing cells within 3 h after serum stimulation. Similar results were obtained when cells were labeled for 10.5 h. About 70% of total polyadenylated mRNA was in the polysome fraction in all growth states regardless of labeling time, indicating that the shift in mRNA distribution was species specific. These results indicate that the content and metabolism of rp mRNA do not change significantly after growth stimulation. The rate of ribosomal protein synthesis appears to be controlled during the resting-growing transition by an alteration of the efficiency of translation of rp mRNA, possibly at the level of protein synthesis initiation.

scholarly journals Rates of protein turnover in vivo and in vitro in ventricular muscle of hearts from fed and starved rats

1984 ◽  
Vol 222 (2) ◽  
pp. 395-400 ◽  
Author(s):  
V R Preedy ◽  
D M Smith ◽  
N F Kearney ◽  
P H Sugden
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Protein Turnover ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Ventricular Muscle ◽  
Degradation Rates ◽  
Perfused Hearts

Starvation of 300 g rats for 3 days decreased ventricular-muscle total protein content and total RNA content by 15 and 22% respectively. Loss of body weight was about 15%. In glucose-perfused working rat hearts in vitro, 3 days of starvation inhibited rates of protein synthesis in ventricles by about 40-50% compared with fed controls. Although the RNA/protein ratio was decreased by about 10%, the major effect of starvation was to decrease the efficiency of protein synthesis (rate of protein synthesis relative to RNA). Insulin stimulated protein synthesis in ventricles of perfused hearts from fed rats by increasing the efficiency of protein synthesis. In vivo, protein-synthesis rates and efficiencies in ventricles from 3-day-starved rats were decreased by about 40% compared with fed controls. Protein-synthesis rates and efficiencies in ventricles from fed rats in vivo were similar to values in vitro when insulin was present in perfusates. In vivo, starvation increased the rate of protein degradation, but decreased it in the glucose-perfused heart in vitro. This contradiction can be rationalized when the effects of insulin are considered. Rates of protein degradation are similar in hearts of fed animals in vivo and in glucose/insulin-perfused hearts. Degradation rates are similar in hearts of starved animals in vivo and in hearts perfused with glucose alone. We conclude that the rates of protein turnover in the anterogradely perfused rat heart in vitro closely approximate to the rates in vivo in absolute terms, and that the effects of starvation in vivo are mirrored in vitro.

scholarly journals Incompatibility of chemical protein synthesis inhibitors with accurate measurement of extended protein degradation rates

2017 ◽  
Vol 5 (5) ◽  
pp. e00359 ◽  
Author(s):  
Christina Chan ◽  
Philip Martin ◽  
Neill J. Liptrott ◽  
Marco Siccardi ◽  
Lisa Almond ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Protein Synthesis Inhibitors ◽  
Degradation Rates ◽  
Chemical Protein Synthesis

scholarly journals Effect of corticosterone treatment on muscle protein turnover in adrenalectomized rats and diabetic rats maintained on insulin

1982 ◽  
Vol 204 (3) ◽  
pp. 663-672 ◽  
Author(s):  
Bhanu R. Odedra ◽  
David J. Millward
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Protein Turnover ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Diabetic Rats ◽  
Constant Infusion ◽  
Degradation Rates ◽  
Adrenalectomized Rats

The effect of corticosterone on protein turnover in skeletal muscle was investigated in growing rats. Protein synthesis was measured in vivo by the constant infusion of [14C]tyrosine. The extent to which any effect of corticosterone is modulated by the hyperinsulinaemia induced by steroid treatment was examined by giving the hormone not only to adrenalectomized rats but also to streptozotocin-induced diabetic rats maintained throughout the treatment period on two dosages of insulin by an implanted osmotic minipump. Approximate rates of protein degradation were also estimated in some cases as the difference between synthesis and net change in muscle protein mass. Measurements were also made of free 3-methylhistidine concentration in muscle and plasma. At 10mg of corticosterone/100g body wt. per day, growth stopped and muscle wasting occurred, whereas at 5 mg of corticosterone/100g body wt. per day no net loss of protein occurred. However, this low dose did induce muscle wasting when insulin concentration was regulated by a dose of 1.2 units/day. Protein synthesis was markedly depressed in all treated groups, the depression in the insulin-maintained rats being marginally more than in the hyperinsulinaemic adrenalectomized rats. The oxidative soleus muscle appeared to be less susceptible to the effect of the corticosterone than was the more glycolytic plantaris or gastrocnemius muscle. Any effect of the corticosterone on protein degradation was much less than its effects on protein synthesis. Where increases in the degradation rates appeared to occur in the rats treated with 10mg of corticosterone/100g body wt. per day, the increases were less than 20%. The free intracellular 3-methylhistidine concentrations were doubled in all groups treated with 5 mg of corticosterone/100g body wt. per day and increased 5-fold in the adrenalectomized rats treated with 10mg of corticosterone/100g body wt. per day, with no change in plasma concentration in any of the groups. It is therefore concluded that: (a) the suppression of protein synthesis is the main effect of glucocorticoids in muscle; (b) marked increases in insulin afford only minor protection against this effect; (c) stimulation of protein degradation may occur, but to a much lesser extent.

scholarly journals Defects in autophagy lead to selective in vivo changes in turnover of cytosolic and organelle proteins in Arabidopsis

2021 ◽  
Author(s):  
Lei Li ◽  
Chun Pong Lee ◽  
Akila Wijerathna-Yapa ◽  
Martyna Broda ◽  
Marisa S. Otegui ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Degradation Rate ◽  
T Complex ◽  
Autophagy Induction ◽  
Degradation Rates ◽  
Specific Proteins ◽  
Protein Degradation Rate ◽  
Synthesis And Degradation

AbstractIdentification of autophagic protein cargo in plants by their abundance in autophagy related genes (ATG) mutants is complicated by changes in both protein synthesis and protein degradation. To detect autophagic cargo, we measured protein degradation rate in shoots and roots of Arabidopsis atg5 and atg11 mutant plants. These data show that less than a quarter of proteins changing in abundance are probable cargo and revealed roles of ATG11 and ATG5 in degradation of specific cytosol, chloroplast and ER-resident proteins, and a specialized role for ATG11 in degradation of proteins from mitochondria and chloroplasts. Our data support a role for autophagy in degrading glycolytic enzymes and the chaperonin containing T-complex polypeptide-1 complex. Autophagy induction by Pi limitation changed metabolic profiles and the protein synthesis and degradation rates of atg5 and atg11 plants. A general decrease in the abundance of amino acids and increase in several secondary metabolites in autophagy mutants was consistent with altered catabolism and changes in energy conversion caused by reduced degradation rate of specific proteins. Combining measures of changes in protein abundance and degradation rates, we also identify ATG11 and ATG5 associated protein cargo of low Pi induced autophagy in chloroplasts and ER-resident proteins involved in secondary metabolism.Single Sentence SummaryProtein cargo of autophagy in plants can be discovered by identifying proteins that increase in abundance and decrease in degradation rate in mutants deficient in autophagy machinery

scholarly journals Targeting the Human 80S Ribosome in Cancer: From Structure to Function and Drug Design for Innovative Adjuvant Therapeutic Strategies

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 629 ◽  
Author(s):  
Arnaud Gilles ◽  
Léo Frechin ◽  
Kundhavai Natchiar ◽  
Giulia Biondani ◽  
Ottilie von Loeffelholz ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Drug Design ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Proliferating Cells ◽  
High Turnover ◽  
Cancer Treatments ◽  
80S Ribosome ◽  
Congenital Diseases ◽  
Risk Of Cancer

The human 80S ribosome is the cellular nucleoprotein nanomachine in charge of protein synthesis that is profoundly affected during cancer transformation by oncogenic proteins and provides cancerous proliferating cells with proteins and therefore biomass. Indeed, cancer is associated with an increase in ribosome biogenesis and mutations in several ribosomal proteins genes are found in ribosomopathies, which are congenital diseases that display an elevated risk of cancer. Ribosomes and their biogenesis therefore represent attractive anti-cancer targets and several strategies are being developed to identify efficient and specific drugs. Homoharringtonine (HHT) is the only direct ribosome inhibitor currently used in clinics for cancer treatments, although many classical chemotherapeutic drugs also appear to impact on protein synthesis. Here we review the role of the human ribosome as a medical target in cancer, and how functional and structural analysis combined with chemical synthesis of new inhibitors can synergize. The possible existence of oncoribosomes is also discussed. The emerging idea is that targeting the human ribosome could not only allow the interference with cancer cell addiction towards protein synthesis and possibly induce their death but may also be highly valuable to decrease the levels of oncogenic proteins that display a high turnover rate (MYC, MCL1). Cryo-electron microscopy (cryo-EM) is an advanced method that allows the visualization of human ribosome complexes with factors and bound inhibitors to improve our understanding of their functioning mechanisms mode. Cryo-EM structures could greatly assist the foundation phase of a novel drug-design strategy. One goal would be to identify new specific and active molecules targeting the ribosome in cancer such as derivatives of cycloheximide, a well-known ribosome inhibitor.

Sign in / Sign up

Export Citation Format

Share Document