Faculty Opinions recommendation of Selective transcriptional regulation by Myc in cellular growth control and lymphomagenesis.

Cell-to-cell heterogeneity prevails in many biological systems, although its origin and function are often unclear. Cell hydrostatic pressure, alias turgor pressure, is essential in physiology and morphogenesis, and its spatial variations are often overlooked. Here, based on a mathematical model describing cell mechanics and water movement in a plant tissue, we predict that cell pressure anticorrelates with cell neighbour number. Using atomic force microscopy, we confirm this prediction in the Arabidopsis shoot apical meristem, a population of stem cells that generate all plant aerial organs. Pressure is predicted to correlate either positively or negatively with cellular growth rate depending on osmotic drive, cell wall extensibility, and hydraulic conductivity. The meristem exhibits one of these two regimes depending on conditions, suggesting that, in this tissue, water conductivity is non-negligible in growth control. Our results illustrate links between local topology, cell mechanical state and cell growth, with potential roles in tissue homeostasis.

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Role of Tyrosine Phosphorylation in Malignant Transformation by Viruses and in Cellular Growth Control

Progress in Nucleic Acid Research and Molecular Biology ◽

10.1016/s0079-6603(08)60450-x ◽

1983 ◽

pp. 221-232 ◽

Cited By ~ 12

Author(s):

Tony Hunter ◽

J.A. Cooper

Keyword(s):

Tyrosine Phosphorylation ◽

Malignant Transformation ◽

Growth Control ◽

Cellular Growth

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Distinct Secreted Frizzled Receptor Protein 1 Staining Pattern in Patients With Hyperplastic Polyposis Coli Syndrome

Archives of Pathology & Laboratory Medicine ◽

10.5858/2004-128-967-dsfrps ◽

2004 ◽

Vol 128 (9) ◽

pp. 967-973

Author(s):

Barbara I. Oberschmid ◽

Wolfgang Dietmaier ◽

Arndt Hartmann ◽

Edgar Dahl ◽

Eva Klopocki ◽

...

Keyword(s):

Mismatch Repair ◽

Staining Pattern ◽

Growth Control ◽

Cellular Growth ◽

Colorectal Carcinogenesis ◽

Receptor Protein ◽

Hyperplastic Polyps ◽

Polyposis Coli ◽

Hyperplastic Polyposis ◽

Mismatch Repair Proteins

Abstract Context.—Patients with hyperplastic polyposis coli syndrome are thought to harbor precursor lesions of a proposed hyperplasia-carcinoma pathway in colorectal cancer, but morphologic recognition of such lesions remains difficult. Hypermethylation of the secreted Frizzled receptor protein 1 gene on chromosome 8p12 is one of the earliest molecular alterations in colorectal carcinogenesis, potentially disrupting the Wnt signaling cascade of cellular growth control. Objective.—To determine if hyperplastic polyps from patients with hyperplastic polyposis coli syndrome show a distinct immunohistochemical expression pattern for mismatch repair proteins and secreted Frizzled receptor protein 1 compared to their sporadic counterparts. Design.—Immunohistochemical studies (secreted Frizzled receptor protein 1, 3 mismatch repair proteins, and p53) were performed on 23 hyperplastic polyps, 6 synchronous colon cancers, and normal colonic mucosa from 6 patients with hyperplastic polyposis coli syndrome and were compared with studies of sporadic hyperplastic polyps obtained from 13 matched control subjects. Results.—The staining pattern for the mismatch repair proteins MLH-1, MSH-2, and MSH-6 did not differ between sporadic and syndromic hyperplastic polyps. In contrast, 52% of syndromic hyperplastic polyps showed a reproducible and distinct staining pattern for secreted Frizzled receptor protein 1 that was not seen in control specimens and that was associated with larger polyp size (P = .002) and location in the proximal colon (P = .01). Conclusions.—Some hyperplastic polyps from patients with hyperplastic polyposis coli syndrome show a secreted Frizzled receptor protein 1 immunophenotype that could indicate alterations of cellular growth control. These findings may help identify precursor lesions in the proposed hyperplasia-carcinoma pathway of colorectal carcinogenesis.

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Immediate early gene-X1 interferes with 26 S proteasome activity by attenuating expression of the 19 S proteasomal components S5a/Rpn10 and S1/Rpn2

Biochemical Journal ◽

10.1042/bj20061072 ◽

2007 ◽

Vol 402 (2) ◽

pp. 367-375 ◽

Cited By ~ 12

Author(s):

Alexander Arlt ◽

Jörg Minkenberg ◽

Marie-Luise Kruse ◽

Frauke Grohmann ◽

Ulrich R. Fölsch ◽

...

Keyword(s):

Growth Control ◽

Immediate Early Gene ◽

Proteasome Activity ◽

Cellular Growth ◽

Early Gene ◽

Immediate Early ◽

Cancer Drug ◽

Mrna Levels ◽

Hek 293 ◽

Human Embryonic Kidney Cells

The stress response gene IEX-1 (immediate early gene-X-1) is involved in the regulation of cell growth and cellular viability. To some extent, these effects include an interference with the proteasomal turnover of certain regulatory proteins. Here, we show that IEX-1 directly attenuates the activity and formation of the 26 S proteasome in HEK-293 cells (human embryonic kidney cells). We further demonstrate that IEX-1 reduces the overall expression levels of certain protein components of the 19 S proteasomal subunit such as S5a/Rpn10 and S1/Rpn2, whereas the expression of other proteasomal proteins was less or not affected. In contrast with direct apoptotic stimuli, such as the anti-cancer drug etoposide, leading to caspase-dependent degradation of S1 and S5a, the effect of IEX-1 is independent of proteolytic cleavage of these proteins. Furthermore, the decreasing effect of IEX-1 on S5a and S1 expression is still seen in the presence of cycloheximide, but not in the presence of actinomycin D, and quantitative real-time PCR revealed lower mRNA levels of S5a and S1 in IEX-1-overexpressing cells, suggesting an interference of IEX-1 with the gene transcription of S5a and S1. Additionally, luciferase assays confirmed an interference of IEX-1 with the activity of the S5a promoter. These findings indicate a role of IEX-1 in the maintenance and assembly of the 26 S proteasome, obviously involving an altered gene expression of certain proteasomal proteins. Thereby, IEX-1 may essentially modulate signalling pathways related to 26 S proteasome activity and involved in cellular growth control and apoptosis.

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Alteration to the SWI/SNF complex in human cancers

Oncology Reviews ◽

10.4081/oncol.2010.89 ◽

2011 ◽

Vol 4 (2) ◽

pp. 89

Author(s):

Vanessa S. Gordon ◽

Colin Rogers ◽

David Reisman

Keyword(s):

Gene Expression ◽

Dna Repair ◽

Cell Adhesion ◽

Growth Control ◽

Cellular Growth ◽

Cancer Development ◽

Catalytic Subunits ◽

Cancer Types ◽

Potential Impact ◽

The Impact

The SWI/SNF complex is a key catalyst for gene expression and regulates a variety of pathways, many of which have anticancer roles. Its central roles in cellular growth control, DNA repair, differentiation, cell adhesion and development are often targeted, and inactivated, during cancer development and progression. In this review, we will discuss what is known about how SWI/SNF is inactivated, and describe the potential impact of abrogating this complex. BRG1 and BRM are the catalytic subunits which are essential for SWI/SNF function, and thus, it is not surprising that they are lost in a variety of cancer types. As neither gene is mutated when lost, the mechanism of suppression, as well as the impact of potential gene activity restoration, are reviewed.

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A multiscale analysis of early flower development in Arabidopsis provides an integrated view of molecular regulation and growth control

10.1101/2020.09.25.313312 ◽

2020 ◽

Author(s):

Yassin Refahi ◽

Argyris Zardilis ◽

Gaël Michelin ◽

Raymond Wightman ◽

Bruno Leggio ◽

...

Keyword(s):

Flower Development ◽

Computational Models ◽

Fundamental Problem ◽

Expression Patterns ◽

Growth Control ◽

Cell Lineage ◽

Time Lapse ◽

Growth Patterns ◽

Cellular Growth ◽

Early Flower

Abstract The link between gene regulation and morphogenesis of multicellular organisms is a fundamental problem in biology. We address this question in the floral meristem of Arabidopsis, which generates new tissues and organs through complex changes in growth patterns. Starting from high-resolution time-lapse images, we generated a comprehensive 4-D atlas of early flower development including cell lineage, cellular growth rates and the expression patterns of 28 regulatory genes. This information was introduced in MorphoNet, a web-based open-access platform. The application of mechanistic computational models indicated that the molecular network based on the literature only explained a minority of the expression patterns. This was substantially improved by adding single regulatory hypotheses for individual genes. We next used the integrated information to correlate growth with the combinatorial expression of multiple genes. This led us to propose a set of hypotheses for the action of individual genes in morphogenesis, not visible by simply correlating gene expression and growth. This identified the central transcription factor LEAFY as a potential regulator of heterogeneous growth, which was supported by quantifying growth patterns in a leafy mutant. By providing an integrated, multiscale view of flower development, this atlas should represent a fundamental step towards mechanistic multiscale-scale models of flower development.

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Quantifying the entropic cost of cellular growth control

10.1101/112748 ◽

2017 ◽

Author(s):

Daniele De Martino ◽

Fabrizio Capuani ◽

Andrea De Martino

Keyword(s):

Growth Control ◽

Growth Dynamics ◽

Cellular Growth ◽

Initial Size ◽

E Coli ◽

Regulatory Strategies ◽

Control Growth ◽

Metabolic States ◽

Scale Models ◽

Genome Scale

We quantify the amount of regulation required to control growth in living cells by a Maximum Entropy approach to the space of underlying metabolic states described by genome-scale models. Results obtained forE. coliand human cells are consistent with experiments and point to different regulatory strategies by which growth can be fostered or repressed. Moreover we explicitly connect the ‘inverse temperature’ that controls MaxEnt distributions to the growth dynamics, showing that the initial size of a colony may be crucial in determining how an exponentially growing population organizes the phenotypic space.

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HRS/SRp40-mediated inclusion of the fibronectin EIIIB exon, a possible cause of increased EIIIB expression in proliferating liver.

Molecular and Cellular Biology ◽

10.1128/mcb.17.7.4096 ◽

1997 ◽

Vol 17 (7) ◽

pp. 4096-4104 ◽

Cited By ~ 44

Author(s):

K Du ◽

Y Peng ◽

L E Greenbaum ◽

B A Haber ◽

R Taub

Keyword(s):

Time Course ◽

Growth Control ◽

Sr Proteins ◽

Mrna Splicing ◽

Cellular Growth ◽

Liver Growth ◽

Alternatively Spliced ◽

Growth Changes ◽

Possible Cause

Serine-arginine (SR)-rich proteins are believed to be important in mediating alternative pre-mRNA splicing. HRS/SRp40 expression is elevated in liver cell proliferation during development, regeneration, and oncogenesis. We tested whether HRS expression correlates with the appearance of alternatively spliced fibronectin transcripts during liver growth. HRS was highly expressed during the proliferative phase of liver development, correlating with expression of the fibronectin EIIIB alternative exon. In regenerating liver, HRS protein was induced in a time course consistent with the observed increase in fibronectin transcripts containing the EIIIB exon, particularly in nonparenchymal liver cells. Furthermore, in an in vivo assay, HRS, and not other SR proteins, directly mediated EIIIB exon inclusion in the fibronectin transcript. This alternative splicing was dependent on a purine-rich region within the EIIIB exon to which HRS specifically bound. We have established that HRS has the potential to contribute to the regulation of fibronectin pre-mRNA splicing during liver growth. Changes in fibronectin forms may be important in modifying liver architecture during the proliferative response, thus providing a potential mechanism by which SR proteins may participate in cellular growth control.

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