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Cell growth

About: Cell growth is a research topic. Over the lifetime, 104237 publications have been published within this topic receiving 3751303 citations. The topic is also known as: GO:0016049 & cellular growth.


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Journal ArticleDOI
TL;DR: It is proposed that Sml1 inhibits dNTP synthesis posttranslationally by binding directly to Rnr1 and that Mec1 and Rad53 are required to relieve this inhibition.

762 citations

Journal ArticleDOI
TL;DR: It is shown that mice deficient for S 6K1 or S6K2 are born at the expected Mendelian ratio, and analysis of S6 phosphorylation in the cytoplasm and nucleoli of cells derived from the distinct S7K genotypes suggests that both kinases are required for full S6osphorylation but that S6k2 may be more prevalent in contributing to this response.
Abstract: Recent studies showed that the 40S ribosomal protein S6 kinase (S6K) p70S6K/p85S6K, termed S6K1 (51), is a major effector of cell growth. This conclusion stems from gene deletion studies with Drosophila (39) and with mice (51) as well as recent studies with cell cultures (11). The loss of the Drosophila S6K (dS6K) gene is semilethal, with the few surviving adults having a severely reduced body size. The larvae of such flies exhibit a long developmental delay, consistent with a twofold increase in cell cycle doubling times. The few surviving adults are quite lethargic, living no longer than 2 weeks, and females are sterile. Surprisingly, the reduction in mass is strictly due to a decrease in cell size rather than to a decrease in cell number (39). In mice, removal of this kinase is not lethal, but the mice are approximately 20% smaller at birth (51). Such mice exhibit normal fasting glucose levels but are mildly glucose intolerant due to markedly reduced levels of circulating insulin (42). Reduced insulin levels are caused by a reduction in pancreatic endocrine mass and an impairment of insulin secretion, which can be traced to a selective reduction in β-cell size. Unexpectedly, the effects on body mass and hypoinsulinemia do not appear to be attributable to a reduction in S6 phosphorylation, as this response proved to be largely intact in S6K1-deficient animals (51). However, S6 phosphorylation in such animals was still sensitive to the bacterial macrolide rapamycin (51), which inhibits the mammalian target of rapamycin (mTOR) (1, 7, 16, 48), the upstream S6K1 kinase (4, 8, 18), suggesting the existence of a second S6K. Subsequent searches of expressed sequence tag databases and biochemical studies led to the identification of S6K2, which exhibited overall homology of over 80% with S6K1 in the highly conserved kinase and linker domains (17, 47, 51). In all tissues examined from S6K1-deficient mice, S6K2 transcripts were upregulated (51). From this observation, it was reasoned that S6K1 and S6K2 functions were redundant and that a deletion of the S6K1 gene led to a compensatory increase in the expression of S6K2. In parallel studies, it was demonstrated that rapamycin suppressed the serum-induced translational upregulation of a family of mRNAs which contain a polypyrimidine tract at their 5′ end (5′-terminal oligopyrimidine [5′TOP] mRNAs) (20, 55). These mRNAs largely code for components of the translational apparatus, most notably, ribosomal proteins (37). Earlier studies had shown that the translation of such transcripts is under selective translational control (22) and requires an intact 5′TOP tract (19, 49). In addition, a dominant interfering allele of S6K1 inhibited the mitogen-induced translational upregulation of 5′TOP mRNAs to the same extent as rapamycin, whereas an activated allele of S6K1, which exhibits a substantial degree of rapamycin resistance, largely protected these transcripts from the inhibitory effects of rapamycin (19, 49). Seemingly consistent with these arguments, in embryonic stem (ES) cells from which S6K1 had been homologously deleted by selection with high doses of G418, serum no longer had an effect on the upregulation of 5′TOP mRNAs, nor was there a redistribution of 5′TOP mRNAs from polysomes to nonpolysomes in the presence of rapamycin (24). However, S6 phosphorylation was initially reported to be abolished in these cells (24), despite the fact that it was largely intact in cells and tissues derived from S6K1−/− mice (51). This difference seemed to be resolved in subsequent studies, where S6 phosphorylation was detected in these same S6K1−/− ES cells and S6K2 was present and active (31, 60). Despite these observations, it was again recently reported that S6 phosphorylation was absent from these same cells (53). Furthermore, it was also claimed in the latter study that S6K activation, S6 phosphorylation, and rapamycin had little impact on 5′TOP mRNA translation in PC12 cells (53), although others working with these same cells had reported earlier that rapamycin treatment abolished the selective recruitment of these transcripts from small to large polysomes (44). Obviously, cells lacking both S6K1 and S6K2 would facilitate such studies. Therefore, we set out to delete the S6K2 gene from mice and to determine whether we could generate S6K1−/−/S6K2−/− mice. Here we report on the deletion of the S6K2 gene and the effects of deleting both S6K1 and S6K2 on animal growth and viability as well as on S6 phosphorylation, cell proliferation, and 5′TOP mRNA translation.

761 citations

Journal ArticleDOI
09 Nov 1984-Science
TL;DR: It is suggested that the growth inhibitor and the type beta transforming growth factor are similar molecules that can either stimulate or inhibit cell proliferation depending on the experimental conditions.
Abstract: Purified growth inhibitor from BSC-1 cells and type beta transforming growth factor from human platelets are shown to have nearly identical biological activity and to compete for binding to the same cell membrane receptor. These findings suggest that the growth inhibitor and the type beta transforming growth factor are similar molecules. The data also show that the same purified polypeptide can either stimulate or inhibit cell proliferation depending on the experimental conditions.

760 citations

Journal ArticleDOI
02 Nov 1990-Cell
TL;DR: TGF-beta induces proliferation of connective tissue cells at low concentrations by stimulating autocrine PDGF-AA secretion, which at higher concentrations of TGF- beta, is decreased by down-regulation of PDGF receptor alpha subunits and perhaps by direct growth inhibition.

760 citations

Journal ArticleDOI
TL;DR: Recent findings on the cellular and molecular mechanisms by which ROS signal events leading to impairment of endothelial barrier function and promotion of leukocyte adhesion are discussed.
Abstract: Reactive oxygen species (ROS) are generated at sites of inflammation and injury, and at low levels, ROS can function as signaling molecules participating as signaling intermediates in regulation of fundamental cell activities such as cell growth and cell adaptation responses, whereas at higher concentrations, ROS can cause cellular injury and death. The vascular endothelium, which regulates the passage of macromolecules and circulating cells from blood to tissues, is a major target of oxidant stress, playing a critical role in the pathophysiology of several vascular diseases and disorders. Specifically, oxidant stress increases vascular endothelial permeability and promotes leukocyte adhesion, which are coupled with alterations in endothelial signal transduction and redox-regulated transcription factors such as activator protein-1 and nuclear factor-κB. This review discusses recent findings on the cellular and molecular mechanisms by which ROS signal events leading to impairment of endothelial barrier fun...

760 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20233,956
20226,245
20215,196
20206,247
20196,050
20185,767