scholarly journals Mechanism for differential sensitivity of the chromosome and growth cycles of mammalian cells to the rate of protein synthesis.

1985 ◽  
Vol 5 (11) ◽  
pp. 2959-2966 ◽  
Author(s):  
R S Wu ◽  
W M Bonner
Keyword(s):  
Protein Synthesis ◽  
Dna Synthesis ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Growth Cycle ◽  
Differential Sensitivity ◽  
G1 Phase ◽  
Histone Protein ◽  
Chromosome Cycle ◽  
Compensation Mechanisms

It has been documented widely that when the generation times of eucaryotic cells are lengthened by slowing the rate of protein synthesis, the duration of the chromosome cycle (S, G2, and M phases) remains relatively invariant. Paradoxically, when the growth of exponentially growing cultures of CHO cells is partially inhibited with inhibitors of protein synthesis, the immediate effect is a proportionate reduction in the rate of total protein, histone protein, and DNA synthesis. However, on further investigation it was found that over the next 2 h the rates of histone protein and DNA synthesis recover, in some cases completely to the uninhibited rate, while the synthesis rates of other proteins do not recover. We called this process chromosome cycle compensation. The amount of compensation seen in CHO cell cultures can account quantitatively for the relative invariance in the length of the chromosome cycle (S, G2, and M phases) reported for these cells. The mechanism for this compensation involves a specific increase in the levels of histone mRNAs. An invariant chromosome cycle coupled with a lengthening growth cycle must result in a disproportionate lengthening of the G1 phase. Thus, these results suggest that chromosome cycle invariance may be due more to specific cellular compensation mechanisms rather than to the more usual interpretation involving a rate-limiting step for cell cycle progression in the G1 phase.

Mechanism for differential sensitivity of the chromosome and growth cycles of mammalian cells to the rate of protein synthesis

1985 ◽  
Vol 5 (11) ◽  
pp. 2959-2966
Author(s):  
R S Wu ◽  
W M Bonner
Keyword(s):  
Protein Synthesis ◽  
Dna Synthesis ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Growth Cycle ◽  
Differential Sensitivity ◽  
G1 Phase ◽  
Histone Protein ◽  
Chromosome Cycle ◽  
Compensation Mechanisms

It has been documented widely that when the generation times of eucaryotic cells are lengthened by slowing the rate of protein synthesis, the duration of the chromosome cycle (S, G2, and M phases) remains relatively invariant. Paradoxically, when the growth of exponentially growing cultures of CHO cells is partially inhibited with inhibitors of protein synthesis, the immediate effect is a proportionate reduction in the rate of total protein, histone protein, and DNA synthesis. However, on further investigation it was found that over the next 2 h the rates of histone protein and DNA synthesis recover, in some cases completely to the uninhibited rate, while the synthesis rates of other proteins do not recover. We called this process chromosome cycle compensation. The amount of compensation seen in CHO cell cultures can account quantitatively for the relative invariance in the length of the chromosome cycle (S, G2, and M phases) reported for these cells. The mechanism for this compensation involves a specific increase in the levels of histone mRNAs. An invariant chromosome cycle coupled with a lengthening growth cycle must result in a disproportionate lengthening of the G1 phase. Thus, these results suggest that chromosome cycle invariance may be due more to specific cellular compensation mechanisms rather than to the more usual interpretation involving a rate-limiting step for cell cycle progression in the G1 phase.

scholarly journals Interrelationships of protein and DNA syntheses during replication of mammalian cells.

1985 ◽  
Vol 5 (6) ◽  
pp. 1279-1286 ◽  
Author(s):  
E Sariban ◽  
R S Wu ◽  
L C Erickson ◽  
W M Bonner
Keyword(s):  
Protein Synthesis ◽  
Dna Synthesis ◽  
Mammalian Cells ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Mrna Levels ◽  
Histone Protein ◽  
Ovary Cells ◽  
Histone Synthesis ◽  
Dna Components

During the replication of chromatin, the syntheses of the histone protein and DNA components are closely coordinated but not totally linked. The interrelationships of total protein synthesis, histone protein synthesis, DNA synthesis, and mRNA levels have been investigated in Chinese hamster ovary cells subjected to several different types of inhibitors in several different temporal combinations. The results from these studies and results reported elsewhere can be brought together into a consistent framework which combines the idea of autoregulation of histone biosynthesis as originally proposed by W. B. Butler and G. C. Mueller (Biochim. Biophys. Acta 294:481-496, 1973] with the presence of basal histone synthesis and the effects of protein synthesis on DNA synthesis. The proposed framework obviates the difficulties of Butler and Mueller's model and may have wider application in understanding the control of cell growth.

Interrelationships of protein and DNA syntheses during replication of mammalian cells

1985 ◽  
Vol 5 (6) ◽  
pp. 1279-1286
Author(s):  
E Sariban ◽  
R S Wu ◽  
L C Erickson ◽  
W M Bonner
Keyword(s):  
Protein Synthesis ◽  
Dna Synthesis ◽  
Mammalian Cells ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Mrna Levels ◽  
Histone Protein ◽  
Ovary Cells ◽  
Histone Synthesis ◽  
Dna Components

During the replication of chromatin, the syntheses of the histone protein and DNA components are closely coordinated but not totally linked. The interrelationships of total protein synthesis, histone protein synthesis, DNA synthesis, and mRNA levels have been investigated in Chinese hamster ovary cells subjected to several different types of inhibitors in several different temporal combinations. The results from these studies and results reported elsewhere can be brought together into a consistent framework which combines the idea of autoregulation of histone biosynthesis as originally proposed by W. B. Butler and G. C. Mueller (Biochim. Biophys. Acta 294:481-496, 1973] with the presence of basal histone synthesis and the effects of protein synthesis on DNA synthesis. The proposed framework obviates the difficulties of Butler and Mueller's model and may have wider application in understanding the control of cell growth.

scholarly journals Primase p49 mRNA expression is serum stimulated but does not vary with the cell cycle.

1989 ◽  
Vol 9 (5) ◽  
pp. 1940-1945 ◽  
Author(s):  
B Y Tseng ◽  
C E Prussak ◽  
M T Almazan
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Small Subunit ◽  
Mrna Levels ◽  
Proliferating Cells ◽  
Restriction Point ◽  
Serum Stimulation ◽  
G1 Cells

Expression of the small-subunit p49 mRNA of primase, the enzyme that synthesizes oligoribonucleotides for initiation of DNA replication, was examined in mouse cells stimulated to proliferate by serum and in growing cells. The level of p49 mRNA increased approximately 10-fold after serum stimulation and preceded synthesis of DNA and histone H3 mRNA by several hours. Expression of p49 mRNA was not sensitive to inhibition by low concentrations of cycloheximide, which suggested that the increase in mRNA occurred before the restriction point control for cell cycle progression described for mammalian cells and was not under its control. p49 mRNA levels were not coupled to DNA synthesis, as observed for the replication-dependent histone genes, since hydroxyurea or aphidicolin had no effect on p49 mRNA levels when added before or during S phase. These inhibitors did have an effect, however, on the stability of p49 mRNA and increased the half-life from 3.5 h to about 20 h, which suggested an interdependence of p49 mRNA degradation and DNA synthesis. When growing cells were examined after separation by centrifugal elutriation, little difference was detected for p49 mRNA levels in different phases of the cell cycle. This was also observed when elutriated G1 cells were allowed to continue growth and then were blocked in M phase with colcemid. Only a small decrease in p49 mRNA occurred, whereas H3 mRNA rapidly decreased, when cells entered G2/M. These results indicate that the level of primase p49 mRNA is not cell cycle regulated but is present constitutively in proliferating cells.

Control of thymidine kinase mRNA during the cell cycle

1987 ◽  
Vol 7 (8) ◽  
pp. 2925-2932
Author(s):  
D L Coppock ◽  
A B Pardee
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Dna Synthesis ◽  
Thymidine Kinase ◽  
Gene Transcription ◽  
Half Life ◽  
Mammalian Cells ◽  
Mrna Degradation ◽  
S Phase ◽  
3T3 Cells

To investigate the mechanism which controls the onset of DNA synthesis, we examined the regulation of thymidine kinase (TK) and its mRNA in the cell cycle. TK activity provides a useful marker for the onset of the S phase in mammalian cells. The present analysis of regulation of TK mRNA in BALB/c 3T3 cells showed that (i) the increase in TK activity depended on the availability of TK mRNA, (ii) the level of TK mRNA between G0 and S increased more than 20-fold, (iii) the rate of run-on TK transcription increased at most 2- to 4-fold between the G0 and S phases, (iv) the half-life of TK mRNA was greater than 8 to 12 h in the S and M phases and decreased as cells entered quiescence, (v) the TK mRNA increase was fully blocked by inhibition of protein synthesis by only 60%, (vi) this inhibition was completely effective for up to about 10 h following serum addition and progressively much less effective when the drugs were added later. These results suggest that the appearance of TK mRNA at the beginning of the S phase in serum-stimulated 3T3 cells is controlled not only by the rate of gene transcription but importantly also by the decreased rate of mRNA degradation. Similar mechanisms may be involved in regulation of the onset of DNA synthesis and the increase in TK mRNA since both are controlled in a manner consistent with a requirement for a labile protein.

Integrins and cell proliferation

2001 ◽  
Vol 114 (14) ◽  
pp. 2553-2560 ◽  
Author(s):  
Martin Alexander Schwartz ◽  
Richard K. Assoian
Keyword(s):  
Cell Cycle ◽  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Integrated Control ◽  
G1 Phase ◽  
Erk Pathway ◽  
Cycle Progression ◽  
Cyclin Dependent Kinases

Cell cycle progression in mammalian cells is strictly regulated by both integrin-mediated adhesion to the extracellular matrix and by binding of growth factors to their receptors. This regulation is mediated by G1 phase cyclin-dependent kinases (CDKs), which are downstream of signaling pathways under the integrated control of both integrins and growth factor receptors. Recent advances demonstrate a surprisingly diverse array of integrin-dependent signals that are channeled into the regulation of the G1 phase CDKs. Regulation of cyclin D1 by the ERK pathway may provide a paradigm for understanding how cell adhesion can determine cell cycle progression.

scholarly journals MACROMOLECULAR SYNTHESES RELATED TO THE REPRODUCTIVE CYST OF TETRAHYMENA PATULA

1973 ◽  
Vol 59 (3) ◽  
pp. 615-623 ◽  
Author(s):  
P. R. Gabe ◽  
L. E. de Bault
Keyword(s):  
Protein Synthesis ◽  
Dna Synthesis ◽  
Generation Time ◽  
Rna Synthesis ◽  
Culture Medium ◽  
Tritiated Thymidine ◽  
Growth Cycle ◽  
The Third ◽  
Rna And Protein Synthesis ◽  
The Mean

Macromolecular syntheses in encysted Tetrahymena patula were studied using Feulgen fluorescence cytophotometry, autoradiography, and inhibitors of RNA and protein synthesis. Cycloheximide significantly depressed protein synthesis and D-actinomycin effectively blocked RNA synthesis. Under these conditions, the cells within the cyst were unable to divide. Both cytophotometric measurements and autoradiographic data with tritiated thymidine show that DNA synthesis does not occur during the encystment divisions. Excysted cells placed in nutrient broth medium showed a prolonged generation time after the first cell growth cycle, and by the third generation the mean DNA content per cell was almost triple that of starved excysted cells. These findings indicate that (a) the encystment divisions require RNA and protein synthesis, which are apparently effected through turnover, (b) the encystment division cycles occur in the absence of DNA synthesis, and (c) excysted cells placed in culture medium may go through more than one DNA replication per cell cycle.

scholarly journals Control of thymidine kinase mRNA during the cell cycle.

1987 ◽  
Vol 7 (8) ◽  
pp. 2925-2932 ◽  
Author(s):  
D L Coppock ◽  
A B Pardee
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Dna Synthesis ◽  
Thymidine Kinase ◽  
Gene Transcription ◽  
Half Life ◽  
Mammalian Cells ◽  
Mrna Degradation ◽  
S Phase ◽  
3T3 Cells

To investigate the mechanism which controls the onset of DNA synthesis, we examined the regulation of thymidine kinase (TK) and its mRNA in the cell cycle. TK activity provides a useful marker for the onset of the S phase in mammalian cells. The present analysis of regulation of TK mRNA in BALB/c 3T3 cells showed that (i) the increase in TK activity depended on the availability of TK mRNA, (ii) the level of TK mRNA between G0 and S increased more than 20-fold, (iii) the rate of run-on TK transcription increased at most 2- to 4-fold between the G0 and S phases, (iv) the half-life of TK mRNA was greater than 8 to 12 h in the S and M phases and decreased as cells entered quiescence, (v) the TK mRNA increase was fully blocked by inhibition of protein synthesis by only 60%, (vi) this inhibition was completely effective for up to about 10 h following serum addition and progressively much less effective when the drugs were added later. These results suggest that the appearance of TK mRNA at the beginning of the S phase in serum-stimulated 3T3 cells is controlled not only by the rate of gene transcription but importantly also by the decreased rate of mRNA degradation. Similar mechanisms may be involved in regulation of the onset of DNA synthesis and the increase in TK mRNA since both are controlled in a manner consistent with a requirement for a labile protein.

scholarly journals A hierarchy of ATP-consuming processes in mammalian cells

1995 ◽  
Vol 312 (1) ◽  
pp. 163-167 ◽  
Author(s):  
F Buttgereit ◽  
M D Brand
Keyword(s):  
Protein Synthesis ◽  
Dna Synthesis ◽  
Mammalian Cells ◽  
Energy Supply ◽  
Proton Leak ◽  
Control Analysis ◽  
Atp Production ◽  
Significant Control ◽  
The Individual ◽  
Strong Control

The rates of different ATP-consuming reactions were measured in concanavalin A-stimulated thymocytes, a model system in which more than 80% of the ATP consumption can be accounted for. There was a clear hierarchy of the responses of different energy-consuming reactions to changes in energy supply: pathways of macromolecule biosynthesis (protein synthesis and RNA/DNA synthesis) were most sensitive to energy supply, followed by sodium cycling and then calcium cycling across the plasma membrane. Mitochondrial proton leak was the least sensitive to energy supply. Control analysis was used to quantify the relative control over ATP production exerted by the individual groups of ATP-consuming reactions. Control was widely shared; no block of reactions had more than one-third of the control. A fuller control analysis showed that there appeared to be a hierarchy of control over the flux through ATP: protein synthesis > RNA/DNA synthesis and substrate oxidation > Na+ cycling and Ca2+ cycling > other ATP consumers and mitochondrial proton leak. Control analysis also indicated that there was significant control over the rates of individual ATP consumers by energy supply. Each ATP consumer had strong control over its own rate but very little control over the rates of the other ATP consumers.

Non-histone protein synthesis during G1 phase and its relation to dna replication

1976 ◽  
Vol 87 (3) ◽  
pp. 277-287 ◽  
Author(s):  
Eugene W. Gerner ◽  
Raymond E. Meyn ◽  
Ronald M. Humphrey
Keyword(s):  
Protein Synthesis ◽  
Dna Replication ◽  
G1 Phase ◽  
Histone Protein
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