Reduction in Fibronectin Expression and Alteration in Cell Morphology Are Coincident in NIH3T3 Cells Expressing a Mutant E2F1 Transcription Factor

Jordan‐Sciutto, Kelly L.; Logan, Thomas J.; Norton, Pamela A.; Derfoul, Assia; Dodge, George R.; Hall, D.

doi:10.1006/excr.1997.3762

Cited by 12 publications

(7 citation statements)

References 29 publications

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“…p300 has been shown to contribute to basal and to TGF-β-stimulated transcription of the collagen type I gene, acting in the latter instance through the SMAD transcriptional activator [40]. p300 also facilitates E2F-1 directed transcription of fibronectin in fibroblasts [41]. Downmodulation of fibronectin by roscovitine could result from its ability to inhibit CDK2/E2F/p300 complexes [42].…”

Section: Discussionmentioning

confidence: 99%

Antifibrotic Effects of Roscovitine in Normal and Scleroderma Fibroblasts

2012

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Heightened production of collagen and other matrix proteins underlies the fibrotic phenotype of systemic sclerosis (SSc). Roscovitine is an inhibitor of cyclin-dependent kinases that promote cell cycling (CDK1, 2), neuronal development (CDK5) and control transcription (CDK7,9). In an in vivo glomerulonephritis model, roscovitine treatment decreased mesangial cell proliferation and matrix proteins [1]. We investigated whether roscovitine could regulate fibrotic protein production directly rather than through cell cycling. Our investigations revealed that roscovitine coordinately inhibited the expression of collagen, fibronectin, and connective tissue growth factor (CTGF) in normal and SSc fibroblasts. This effect occurred on a transcriptional basis and did not result from roscovitine-mediated cell cycle inhibition. Roscovitine-mediated suppression of matrix proteins could not be reversed by the exogenous profibrotic cytokines TGF-β or IL-6. To our knowledge, we are the first to report that roscovitine modulates matrix protein transcription. Roscovitine may thus be a viable treatment option for SSc and other fibrosing diseases.

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Section: Discussionmentioning

confidence: 99%

Antifibrotic Effects of Roscovitine in Normal and Scleroderma Fibroblasts

2012

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“…Cellular FN plays a role in attachment, spreading, and shape, and also aects aspects of cell proliferation (Jordan-Sciutto et al 1997). The mechanism by which FN is incorporated into the extracellular matrix is unclear, although integrin receptors appear to be involved in this process (Ramos et al 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Recent ®ndings indicate that the concentration of Sp1, which competes with G10BP for binding to the G-rich sequences, is of particular importance and determines the expression level of the FN gene . Another transcription factor is E2F1, which is known to regulate cell shape and cell proliferation, producing reduced amounts of FN-mRNA and protein by modu-lating the 5¢-¯anking region of the FN gene (Jordan-Sciutto et al 1997).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional repression of the human fibronectin gene in laryngeal squamous cell carcinoma cells

Görögh

Maune

Lippert

et al. 2001

Journal of Cancer Research and Clinical Oncology

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“…Aliquots of the medium were added to two volumes of ice-cold acetone, and the proteins were precipitated at Ϫ20°C, as by Jordan-Sciutto et al (28). The protein precipitate was pelleted by centrifugation at 14,000 ϫ g for 10 min at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Cartilage Oligomeric Matrix Protein Protects Cells against Death by Elevating Members of the IAP Family of Survival Proteins

Gagarina

Carlberg

Mouriès

et al. 2008

Journal of Biological Chemistry

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Cartilage oligomeric matrix protein (COMP) is a component of cartilage, synovium, ligament, and tendon, yet its normal function is largely unknown. To identify its function we have expressed it in 293 and HeLa cell lines and in primary human chondrocytes. We find that COMP protects these cells against death, either in the presence or absence of tumor necrosis factor ␣ and is able to block activation of caspase 3, a critical effector caspase. This effect appears to be mediated by the IAP (inhibitor of apoptosis protein) family of anti-apoptotic proteins because the levels of XIAP, survivin, cIAP1 and cIAP2 are significantly elevated in the COMP-expressing cells and down-regulation of survivin and XIAP protein levels by small interfering RNAs blocks the ability of COMP to enhance survival. The mRNAs for most of the IAP family members were not increased by COMP, indicating that a translational/post-translational mechanism was involved in their induction. However, in both HeLa cells and chondrocytes, COMP induced survivin mRNA by 5-fold. Thus survivin is the first gene identified to be up-regulated transcriptionally by COMP. The carboxyl-terminal half of the protein comprising the type 3 repeats and the RGD sequence (CaCTD domain) was sufficient to promote survival and to elevate the IAPs. Further, an RGD peptide was able to block the prosurvival effect of COMP and the induction of XIAP and survivin, indicating that survival is likely mediated through integrin signaling. These data point to a new role for COMP in protecting cells against death.

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Reduction in Fibronectin Expression and Alteration in Cell Morphology Are Coincident in NIH3T3 Cells Expressing a Mutant E2F1 Transcription Factor

Cited by 12 publications

References 29 publications

Antifibrotic Effects of Roscovitine in Normal and Scleroderma Fibroblasts

Antifibrotic Effects of Roscovitine in Normal and Scleroderma Fibroblasts

Transcriptional repression of the human fibronectin gene in laryngeal squamous cell carcinoma cells

Cartilage Oligomeric Matrix Protein Protects Cells against Death by Elevating Members of the IAP Family of Survival Proteins

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