Transforming Growth Factor-β (TGF-β)-induced Down-regulation of Cyclin A Expression Requires a Functional TGF-β Receptor Complex

Feng, Xin‐Hua; Filvaroff, Ellen; Derynck, Rik

doi:10.1074/jbc.270.41.24237

Cited by 146 publications

(133 citation statements)

References 66 publications

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“…To evaluate this possibility, an expression vector encoding a dominant-negative type II TGF-␤ receptor, which has its cytoplasmic domain truncated, was cotransfected with the PAI-1 reporter gene. This type of dominant-negative construct has previously been shown to block TGF-␤-initiated signal transduction by preventing phosphorylation of type I TGF-␤ receptors by type II TGF-␤ receptors (42). Expression of this dominant-negative receptor reduced activation of the PAI-1 promoter by TGF-␤ from 4.4 ± 1.1-to 1.2 ± 0.2-fold (P < 0.05) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Glucosamine activates the plasminogen activator inhibitor 1 gene promoter through Sp1 DNA binding sites in glomerular mesangial cells.

2000

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Increased flux through the hexosamine biosynthetic pathway is associated with altered gene expression. To investigate the underlying mechanisms, we treated glomerular mesangial cells with glucosamine and studied the regulation of the plasminogen activator inhibitor (PAI)-1 gene. Incubating mesangial cells with 2 mmol/l glucosamine for 4 days resulted in a 3.1 ± 0.4-fold increase in PAI-1 mRNA levels (P < 0.01) and a 33 ± 9-fold increase in the activity of a transiently transfected PAI-1 promoter-luciferase reporter gene (P < 0.01). Cotransfection of an expression vector for a dominant-negative type II TGF-␤ receptor with the PAI-1 promoter-reporter gene did not interfere with this effect of glucosamine. However, mutation of 2 putative Sp1 sites in the PAI-1 promoter, at -76 to -71 and -44 to -39, markedly reduced induction of PAI-1 luciferase activity by glucosamine, from 8.9 ± 1.9-fold to 1.7 ± 0.5-fold (P < 0.01). An electrophoretic mobility shift assay demonstrated that glucosamine increased Sp1 DNA binding by 31 ± 11% (P < 0.05), implying that the effects of glucosamine were explained, in part, by changes in Sp1 DNA binding. High glucose (20 mmol/l) also activated the transiently transfected PAI-1 promoter (2.5 ± 0.4-fold). This effect was diminished by mutation of both the PAI-1 promoter Sp1 sites (1.2 ± 0.3-fold, P < 0.05). In addition, 6-diazo-5-oxo-L-norleucine, a glutamine:fructose-6-phosphateamidotransferase inhibitor, blocked the induction by high glucose (4.7 ± 0.8-to 0.9 ± 0.1-fold, P < 0.01). These results indicate that stimulation of the PAI-1 promoter by both high glucose and glucosamine involves Sp1 and that the hexosamine pathway may be involved in the regulation of gene expression by high glucose in glomerular mesangial cells. Diabetes 49:863-871, 2000

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Section: Resultsmentioning

confidence: 99%

Glucosamine activates the plasminogen activator inhibitor 1 gene promoter through Sp1 DNA binding sites in glomerular mesangial cells.

2000

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“…Upon ligand binding, the intrinsic serine/threonine kinase of TGFbRII phosphorylates TGFbRI to activate its serine/threonine kinase activity (Wrana et al, 1994;Chen and Weinberg, 1995). This activated receptor complex transduces TGFb signals (Feng et al, 1995). Deletion of the serine/threonine kinase domain of TGFbRII produces a dominant negative form (DbRII), which is able to block the growth inhibitory function of TGFb in vitro (Chen et al, 1993;Wieser et al, 1993) and in transgenic animals (Wang et al, 1997b;Bottinger et al, 1997;Gorska et al, 1998), suggesting that TGFbRII is required to mediate the growth inhibitory e ect of TGFb.…”

Section: Introductionmentioning

confidence: 99%

Aberrant cell cycle progression contributes to the early-stage accelerated carcinogenesis in transgenic epidermis expressing the dominant negative TGFβRII

Zhong

et al. 2000

Oncogene

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Mutations in the transforming growth factor b type II receptor (TGFbRII) have been found in various malignant tumors, suggesting that loss of TGFb signaling plays a causal role in late-stage cancer development. To test whether loss of TGFbRII is involved in early-stage carcinogenesis, we have generated transgenic mice expressing a dominant negative TGFbRII (DbRII) in the epidermis. These mice exhibited an increased susceptibility to chemical carcinogenesis protocols at both early and late stages. In the current study, parameters for cell cycle progression and chromosome instability were analysed in DbRII tumors. DbRII papillomas showed an increased S phase in¯ow cytometry. Bromodeoxyuridine (BrdU) labeling and mitotic indices in DbRII papillomas also showed a threefold increase compared to papillomas developing in non-transgenic mice. When papillomas further progressed to squamous cell carcinomas (SCC), both control and DbRII SCC showed similar BrdU labeling indices and percentages of S phase cells. However, DbRII SCC cells showed a sixfold increase in the G2/M population. Mitotic indices in DbRII SCC also showed a threefold increase compared to non-transgenic SCC. Consistent with a perturbed cell cycle, DbRII papillomas and SCC showed reduced expression of the TGFb target genes p15 (INK4b), p21 (WAF-1) and p27 (Kip1), inhibitors of cyclin-dependent kinases (cdks). However, most DbRII papilloma cells exhibited normal centrosome numbers, and DbRII SCC exhibited a similar extent of centrosome abnormalities compared to control SCC (35 ± 40% cells). Most of DbRII SCC exhibited diploid chromosome pro®les. These data indicate that inactivation of TGFbRII accelerates skin tumorigenesis at early stages by the acceleration of loss of cell cycle control, but not by increased chromosome instability. Oncogene (2000) 19, 3623 ± 3631.

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“…In PC12 cells FGF causes a drastic increase in the G1 phase-specific cyclin D1 (Yan and Ziff, 1995). In epithelial cells (Feng et al, 1995) and in Chinese hamster lung fibroblasts (Barlat et al, 1995), TGF-b inhibits the G2-phase specific cyclin A. Moreover, in two colon cancer cell lines (LS1034 and LS513) TGF-b induces increased levels of WAF1/Cip1/p21, a potent inhibitor of various cyclin-cdk activities (Pines, 1994).…”

Section: Type Of Colonymentioning

confidence: 99%

Mitogenic and anti‐proliferative signals for neural crest cells and the neurogenic action of TGF‐β1

1997

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The influence of pertinent growth factors on proliferation and differentiation of quail neural crest cell was assessed by in vitro colony assay in a serum-free (0.5% chick embryo-extract supplemented) culture medium. The factors tested included basic fibroblast growth factor (bFGF; FGF-2), neurotrophins, and transforming growth factor-beta-1 (TGF-b). Both bFGF and neurotrophins are implicated in the development of the peripheral nervous system, whereas TGF-b can affect cell differentiation and modulate the action of other growth factors. Bromodeoxyuridine (BrdU) incorporation indicated that bFGF is mitogenic to pluripotent neural crest cells (and/or their immediate progeny) and to committed melanogenic cells. However, this was not reflected in an increase in colony size. In contrast, colony size did increase when nerve growth factor (NGF) was present in addition to bFGF. This indicated either that both factors are required to initiate cell proliferation or that at least some bFGF-exposed cells become dependent on neurotrophins for survival. Sequential addition of the factors showed that exposure to bFGF was required prior to the presence of a neurotrophin, thus favoring the latter possibility. All three neurotrophins tested, NGF, brainderived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), were capable of supporting survival of pluripotent neural crest cells (or their closely related progeny) in the presence of bFGF. In the absence of bFGF, neurotrophins did not affect colony size. Although the BrdU data indicated that bFGF is also a mitogen for committed melanogenic cells, the size of pigmented colonies did not change in the presence of bFGF alone or of bFGF plus a neurotrophin. This suggested that another, yet to be determined, factor is required for the survival of proliferating melanogenic cells.

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Transforming Growth Factor-β (TGF-β)-induced Down-regulation of Cyclin A Expression Requires a Functional TGF-β Receptor Complex

Cited by 146 publications

References 66 publications

Glucosamine activates the plasminogen activator inhibitor 1 gene promoter through Sp1 DNA binding sites in glomerular mesangial cells.

Glucosamine activates the plasminogen activator inhibitor 1 gene promoter through Sp1 DNA binding sites in glomerular mesangial cells.

Aberrant cell cycle progression contributes to the early-stage accelerated carcinogenesis in transgenic epidermis expressing the dominant negative TGFβRII

Mitogenic and anti‐proliferative signals for neural crest cells and the neurogenic action of TGF‐β1

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