E1A-responsive elements for repression of rat fibronectin gene transcription.

Nakajima, Takuma; Nakamura, Toshio; Tsunoda, Shiho; Nakada, Susumu; Oda, Kinichiro

doi:10.1128/mcb.12.6.2837

Cited by 44 publications

(43 citation statements)

References 54 publications

(62 reference statements)

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“…Mechanical wounding, a nonspecific but powerful stimulus, did not induce FN synthesis in pAEC AA cells. Analysis of the FN promoter revealed a number of transcription factor consensus sequences, such as Sp1, GRE, CRE, and ATF-2 sequences (27,(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61). However, activation of these binding sites after treatment with transforming growth factor-b1, dexamethasone, phorbol-12-myristate-13-acetate, or homocysteine also failed to increase FN expression.…”

Section: Discussionmentioning

confidence: 99%

Decreased Fibronectin Production Significantly Contributes to Dysregulated Repair of Asthmatic Epithelium

Kicic¹,

Hallstrand²,

Sutanto³

et al. 2010

Am J Respir Crit Care Med

137

154

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Rationale: Damage to airway epithelium is followed by deposition of extracellular matrix (ECM) and migration of adjacent epithelial cells. We have shown that epithelial cells from children with asthma fail to heal a wound in vitro. Objectives: To determine whether dysregulated ECM production by the epithelium plays a role in aberrant repair in asthma. Methods: Airway epithelial cells (AEC) from children with asthma (n 5 36), healthy atopic control subjects (n 5 23), and healthy nonatopic control subjects (n 5 53) were investigated by microarray, gene expression and silencing, transcript regulation analysis, and ability to close mechanical wounds. Measurements and Main Results: Time to repair a mechanical wound in vitro by AEC from healthy and atopic children was not significantly different and both were faster than AEC from children with asthma. Microarray analysis revealed differential expression of multiple gene sets associated with repair and remodeling in asthmatic AEC. Fibronectin (FN) was the only ECM component whose expression was significantly lower in asthmatic AEC. Expression differences were verified by quantitative polymerase chain reaction and ELISA, and reduced FN expression persisted in asthmatic cells over passage. Silencing of FN expression in nonasthmatic AEC inhibited wound repair, whereas addition of FN to asthmatic AEC restored reparative capacity. Asthmatic AEC failed to synthesize FN in response to wounding or cytokine/ growth factor stimulation. Exposure to 59, 29deoxyazacytidine had no effect on FN expression and subsequent analysis of the FN promoter did not show evidence of DNA methylation. Conclusions: These data show that the reduced capacity of asthmatic epithelial cells to secrete FN is an important contributor to the dysregulated AEC repair observed in these cells.

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Section: Discussionmentioning

confidence: 99%

Decreased Fibronectin Production Significantly Contributes to Dysregulated Repair of Asthmatic Epithelium

Kicic¹,

Hallstrand²,

Sutanto³

et al. 2010

Am J Respir Crit Care Med

137

154

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“…SV40 large T antigen expression plasmid, SV0ri9-8-16, was obtained from DNA Bank, Tsukuba Life Science Center, RIKEN. E1A expression plasmid, pAd2-12S.E.1A (22), were kindly provided by Dr. Oda (Science University of Tokyo).…”

Section: Methodsmentioning

confidence: 99%

Significance of Nuclear Relocalization of ERK1/2 in Reactivation of c-fos Transcription and DNA Synthesis in Senescent Fibroblasts

Kim‐Kaneyama

Nose

Shibanuma

2000

Journal of Biological Chemistry

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Two of mitogen-activated protein kinases (MAPK), p44mapk /p42 mapk extracellular signal-regulated kinases (ERK1/2), translocate into nuclei following activation and play critical roles in connecting the signal to gene expression and allowing cell-cycle entry. Here we found that the nuclear translocation of ERK1/2 in response to growth stimuli was significantly inhibited in senescent cells that were irreversibly growth arrested, compared with presenescent cells. The activation step of these enzymes was not impaired, since ERK1/2 were phosphorylated and activated in senescent cells as efficiently as in presenescent cells. By elaborately localizing ERK2 in the nuclei of senescent cells, we could restore c-fos transcriptional activity upon growth stimuli, which was repressed in senescent cells. Furthermore, the nuclear localization of ERK1/2 has been suggested to potentiate the proliferative activity of the senescent cells in collaboration with adenovirus E1A protein. More importantly, SV40 large T antigen, the strong inducer of DNA synthesis, had the inherent ability to restore nuclear relocalization of active ERK1/2 in senescent cells, which was essentially required for the reinitiation of DNA synthesis. Thus, manipulating the relocalization of ERK1/2 into nuclei was expected to open the way to overcome some of the senescent phenotypes.

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“…The elevation of the expression level of G10BP-1 may exclude the binding of Sp1 to these sites after mid-G 1 and suppresses FN promoter activity. E1A mutants dl646N and dl922/947 (47), containing deletions of codons 30 to 85 and 122 to 129, respectively, lose the ability to repress FN gene expression (34). Since these regions are essential for binding of E1A to the retinoblastoma protein (pRB) and related proteins p107 and p130 (46,47), the expression of G10BP-1 might be repressed by pRB family members and E1A may overcome this repression through complex formation with pRB family members.…”

Section: Discussionmentioning

confidence: 99%

Cloning and Characterization of a GC-Box Binding Protein, G10BP-1, Responsible for Repression of the Rat Fibronectin Gene

Oda

Shirasuna

Suzuki

et al. 1998

Molecular and Cellular Biology

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Fibronectin (FN) is an extracellular matrix protein that connects the extracellular matrix to intracellular cortical actin filaments through binding to its cell surface receptor, ␣5␤1, a member of the integrin superfamily. The expression level of FN is reduced in most tumor cells, facilitating their anchorage-independent growth by still unclarified mechanisms. The cDNA clone encoding G-rich sequence binding protein G10BP-1, which is responsible for repression of the rat FN gene, was isolated by using a yeast one-hybrid screen with the G10 stretch inserted upstream of the HIS3 and lacZ gene minimal promoters. G10BP-1 comprises 385 amino acids and contains two basic regions and a putative zipper structure. It has the same specificity of binding to three G-rich sequences in the FN promoter and the same size as the G10BP previously identified in adenovirus E1A-and E1B-transformed rat cells. Expression of G10BP-1 is cell cycle regulated; the level was almost undetectable in quiescent rat 3Y1 cells but increased steeply after growth stimulation by serum, reaching a maximum in late G 1 . Expression of FN mRNA is inversely correlated with G10BP-1 expression, and the level decreased steeply during G 1 -to-S progression. This down regulation was strictly dependent on the downstream GC box (GCd), and base substitutions within GCd abolished the sensitivity of the promoter to G10BP-1. In contrast, the level of Sp1, which competes with G10BP for binding to the G-rich sequences, was constant throughout the cell cycle, suggesting that the concentration of G10BP-1 relative to that of Sp1 determines the expression level of the FN gene. Preparation of glutathione S-transferase pulldowns of native proteins from the cell extracts containing exogenously or endogenously expressed G10BP-1, followed by Western blot analysis, showed that G10BP-1 forms homodimers through its basic-zipper structure.Fibronectin (FN) is a large glycoprotein of the extracellular matrix that binds to its cell surface receptor, ␣5␤1, a member of the integrin superfamily, as a dimer (2,15,39). FN consists of multiple rodlike domains, and each domain binds to a component of the extracellular matrix such as collagen and heparin and to its receptor (16). The cytoplasmic domain of the receptor binds to bundles of actin filaments known as stress fibers indirectly through binding to the attachment proteins (14). The binding of FN to its receptor at so-called focal contact sites therefore connects the cytoskeleton with the extracellular matrix (3, 17, 21, 39), governing cell shape, adhesion, and movement. FN is also involved in the regulation of cell proliferation and differentiation through organization of the extracellular matrix and cytoskeleton (7, 15).The expression level of FN is closely linked to the growth potential of cells. The level increases when cells cease growing, and senescent cells inevitably express FN at high levels (11,28,33). On the contrary, FN expression is greatly inhibited upon neoplastic transformation (10,20,35), and most tumor cells express ...

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E1A-responsive elements for repression of rat fibronectin gene transcription.

Cited by 44 publications

References 54 publications

Decreased Fibronectin Production Significantly Contributes to Dysregulated Repair of Asthmatic Epithelium

Decreased Fibronectin Production Significantly Contributes to Dysregulated Repair of Asthmatic Epithelium

Significance of Nuclear Relocalization of ERK1/2 in Reactivation of c-fos Transcription and DNA Synthesis in Senescent Fibroblasts

Cloning and Characterization of a GC-Box Binding Protein, G10BP-1, Responsible for Repression of the Rat Fibronectin Gene

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