Regulation of adherens junction protein expression in growth-activated 3T3 cells and in regenerating liver

Glück, Ursula; Fernández, JoséLuis Rodríguez; Pankov, Roumen; Ben-Ze’ev, Avri

doi:10.1016/0014-4827(92)90102-e

Cited by 46 publications

(21 citation statements)

References 41 publications

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“…We have studied a-actinin, since it is a major component involved in microfilament stabilization and in linking microfilaments to AJs (34). In addition, a-actinin expression is modulated during growth activation and differentiation (21)(22)(23)(24) and is significantly decreased in SVT2 cells. The relationship between a-actinin expression and the tumorigenic phenotype was addressed directly by elevating a-actinin levels in tumor cells that express diminished amounts of this protein.…”

Section: Discussionmentioning

confidence: 99%

“…Although a-actinin is a major and stable cellular protein, recent studies have demonstrated that its expression is regulated under various conditions. For example, after serum stimulation of quiescent 3T3 cells and in regenerating liver, the expression of a-actinin is elevated (21). In contrast, during steroidogenesis (22,23) and adipogenesis (24), a-actinin synthesis is reduced.…”

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confidence: 99%

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Suppression of tumorigenicity in simian virus 40-transformed 3T3 cells transfected with alpha-actinin cDNA.

Glück

Kwiatkowski

Ben-Ze’ev

1993

Proc. Natl. Acad. Sci. U.S.A.

140

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Human cytoskeletal a-actinin cDNA was transfected into highly malignant simian virus 40-transformed BALB/c 3T3 (SVT2) cells that express 6-fold lower levels of a-actinin than nontransformed BALB/c 3T3 cells. SVT2 clones expressing various levels of a-actinin were isolated and their structure and tumorigenic properties were determined. Transfected SVT2 clones expressing a-actinin at levels found in nontumorigenic 3T3 cells displayed a flatter phenotype, a decreased ability to grow in suspension culture in soft agar, and a marked reduction in their ability to form tumors in syngeneic BALB/c mice and in athymic nude mice. Clones overexpressing a-actinin at the highest level (about 2-fold higher than 3T3 cells) were completely suppressed in their ability to form tumors in syngeneic BALB/c mice. The results suggest that a-actinin, an actin-crosslinking protein that is also localized in cell junctions, may have an effective suppressive ability on the transformed phenotype.Malignant transformation of cells is characterized by alterations in cell growth, adhesion, motility, and cell shape (1). Among the more conspicuous morphological alterations in transformed cells are a round phenotype and a decrease in the number of microfilament bundles (2, 3). The disorganization of the actin filaments in transformed cells is often associated with a reduced expression of microfilament proteins such as tropomyosin (4), gelsolin (5), and vinculin (6). These changes in microfilaments correlate with the ability of cells to grow in suspension in semisolid medium (7).Previous studies have demonstrated a reversion in the transformed phenotype of cancer cells in the presence of a variety of agents and a return to the original malignant behavior upon their removal (8). This "reverse transformation" includes a reversible modulation in cell shape and the organization of the cytoskeleton (9). However, the relationships between the changes in growth properties and the altered cell structure of transformed cells are still unknown (10). Do the characteristic changes in cell morphology of transformed cells result from alterations in the rate of growth or are changes in cell adhesion and cytostructure responsible for disruption of the adhesion-dependent growth control? In this study we addressed this question directly by modulating the expression ofa single actin-associated protein a-actinin in a tumorigenic cell line and determined the consequences of altered a-actinin expression on the phenotype of the cells. a-Actinin is an abundant cytoplasmic actin-binding protein (11) that crosslinks actin filaments in vitro and is found in both muscle and nonmuscle cells (12,13). In striated muscle cells, a-actinin is localized in Z-disks; in smooth muscle cells, it is in dense plaques; and in nonmuscle cells, a-actinin is found along microfilaments (14) and in adherens junctions (AJs), at sites where actin filaments attach to the membrane (15)(16)(17). The role of a-actinin in mediating actin attachment to the membrane is not completely understood. ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Suppression of tumorigenicity in simian virus 40-transformed 3T3 cells transfected with alpha-actinin cDNA.

Glück

Kwiatkowski

Ben-Ze’ev

1993

Proc. Natl. Acad. Sci. U.S.A.

140

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“…Both wild type and ␤ sm -actin gene transfections can change both the protein and mRNA levels of endogenous actins, selective tropomyosins, vinculin, talin, and now ADF (6,10,11,31). In contrast, transfection of gene constructs encoding vinculin, ␣-actinin, Tm-1, and gelsolin, which all impact on cell morphology, do not affect the expression of other microfilament associated products (12,13,15,16). This therefore raises the question of whether actin expression is a master regulator of other microfilament components and can send signals to, but does not respond to, the expression of these other gene products.…”

Section: Table I Distribution Of Actin Isoforms In the Unassembled Anmentioning

confidence: 99%

“…In addition, changes in actin and vinculin expression in response to drug treatment are independent of changes in cell shape (8). High level expression of tropomyosin Tm1 (12), vinculin (13,14), ␣-actinin (15), and gelsolin (16), which all alter cell morphology, have no impact on the expression of other microfilament proteins. This suggests that the ability of actin to reprogram expression of microfilament proteins may be unique to actin.…”

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confidence: 99%

Differential Regulation of Actin Depolymerizing Factor and Cofilin in Response to Alterations in the Actin Monomer Pool

Minamide

Painter

Schevzov

et al. 1997

Journal of Biological Chemistry

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Myoblasts, transfected with a human gene encoding a ␤-actin point mutation, down-regulate expression of actin depolymerizing factor (ADF) and its mRNA. Regulation is posttranscriptional. Expression of cofilin, a structurally similar protein, and profilin, CapG, and tropomodulin is not altered with increasing mutant ␤-actin expression. Myoblasts expressing either human ␥-actin or the mutant ␤-actin down-regulate the endogenous mouse actin genes to keep a constant level of actin mRNA, whereas the ␥-actin transfectants do not downregulate ADF. Thus, ADF expression is regulated differently from actin expression.The mutant ␤-actin binds to ADF with about the same affinity as normal actin; however, it does not assemble into normal actin filaments. The decrease in ADF expression correlates with an increase in the unassembled actin pool. When the actin monomer pool in untransfected myoblasts is increased 70% by treatment with latrunculin A, synthesis of ADF and actin are downregulated compared with cofilin and 19 other proteins selected at random. Increasing the actin monomer pool also results in nearly complete phosphorylation of both ADF and cofilin. Thus, ADF and cofilin are coordinately regulated by posttranslational modification, but their expression is differentially regulated. Furthermore, expression of ADF is responsive to the utilization of actin by the cell.

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“…In the adult liver, nonproliferative hepatocytes produce almost all of the plasma forms of fibronectin (24) which do not contain the EIIIA (EDA and ED1) and EIIIB (EDB) exons. The fibronectin gene is induced as a delayed-early gene, and its elevated expression is prolonged up to 48 h posthepatectomy during liver regeneration (13,32). EIIIA and EIIIB exon inclusion in the fibronectin transcript has not been examined before 12 h posthepatectomy (3), when many of the early G 1 events have already occurred.…”

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confidence: 99%

HRS/SRp40-Mediated Inclusion of the Fibronectin EIIIB Exon, a Possible Cause of Increased EIIIB Expression in Proliferating Liver

Peng

Greenbaum

et al. 1997

Molecular and Cellular Biology

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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.The splicing factor HRS (hepatic arginine-serine protein) is expressed in proliferating liver cells. HRS is induced as an immediate-early gene in insulin-treated, mitogen-activated rat hepatoma H35 cells and in our study represented 12% of all insulin-induced cDNAs (7). HRS is a delayed-early gene in regenerating liver and is expressed at a very high level during liver development when the liver is rapidly proliferating (7, 46; reviewed in reference 9). HRS belongs to the serine-arginine (SR) protein family, which is comprised of at least nine structurally related proteins, including SRp20, SRp30a (SF2/ASF), SRp30b (SC35), SRp40, SRp55, and SRp75 (11,12,27,31,39,[52][53][54]. Comparing the partial sequence of human SRp40 and HRS sequence revealed that HRS is rat SRp40 (7, 52). Recently, the human homolog of HRS was identified and shown to have properties of other splicing factors in both in vitro and in vivo splicing assays (39).Pre-mRNA alternative splicing provides an important mechanism of gene and protein expression regulation (19,29,31,40). Through alternative splicing, one primary transcript can generate multiple proteins which may have different functions. Alternative splicing occurs via several pathways, including skipped exons, included introns, alternative 5Ј splice sites, alternative 3Ј splice sites, and mutually exclusive exons. SR proteins have been shown to play essential roles in both constitutive pre-mRNA splicing and regulation of pre-mRNA alternative splicing. In vitro and in vivo splicing assays indicate that SR proteins regulate alternative splicing by promoting the use of proximal 5Ј splice sites (10,23,26,55), and different SR proteins have distinct abilities to regulate alternative splicing of various model pr...

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Regulation of adherens junction protein expression in growth-activated 3T3 cells and in regenerating liver

Cited by 46 publications

References 41 publications

Suppression of tumorigenicity in simian virus 40-transformed 3T3 cells transfected with alpha-actinin cDNA.

Suppression of tumorigenicity in simian virus 40-transformed 3T3 cells transfected with alpha-actinin cDNA.

Differential Regulation of Actin Depolymerizing Factor and Cofilin in Response to Alterations in the Actin Monomer Pool

HRS/SRp40-Mediated Inclusion of the Fibronectin EIIIB Exon, a Possible Cause of Increased EIIIB Expression in Proliferating Liver

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