TIEG1 facilitates transforming growth factor‐β‐mediated apoptosis in the oligodendroglial cell line OLI‐neu

Bender, Herdis; Wang, Ziyuan; Schuster, Norbert; Krieglstein, Kerstin

doi:10.1002/jnr.10856

Cited by 33 publications

(27 citation statements)

References 34 publications

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“…Because biological processes mostly involve additive events, TGF-b might lead to further events besides Fractin generation to completely induce apoptosis. Such an event is the Tieg1-induced down-regulation of Bcl-xl mRNA (Bender et al, 2004). Further analyses are required to clarify additive effects.…”

Section: Discussionmentioning

confidence: 97%

Involvement of fractin in TGF‐β‐induced apoptosis in oligodendroglial progenitor cells

Schulz

Vogel

Mashima

et al. 2009

Glia

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Transforming growth factor-beta (TGF-beta) induces apoptotic cell death during the development of the nervous system. We recently identified that TGF-beta induced apoptosis in oligodendroglial progenitor cells (primary cells as well as oligodendroglial cell line OLI-neu) is characterized by down-regulation of Bcl-xl. In this report, we now focused on mechanisms that mediate TGF-beta dependent Bcl-xl down-regulation in oligodendroglial cells. We showed that the caspase-specific cleavage product Fractin is produced in oligodendroglial cells during TGF-beta-mediated apoptosis, which represents an early event of the cascade. Cleavage of actin into Fractin was dependent on functional actin and caspases, and occurred simultaneously with a Fractin-Bcl-xl-interaction. This Fractin-Bcl-xl interaction indicated a connection between Bcl-xl down-regulation and Fractin appearance, since Bcl-xl regulation was also dependent on caspases and functional actin, and an overexpression of Fractin induced a Bcl-xl protein down-regulation. Further analysis of Fractin-Bcl-xl interaction in other culture systems confirmed these data. In conclusion, we show that Fractin is not only an apoptotic marker, but has indeed a functional role in apoptotic signaling in oligodendrocytes.

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Section: Discussionmentioning

confidence: 97%

Involvement of fractin in TGF‐β‐induced apoptosis in oligodendroglial progenitor cells

Schulz

Vogel

Mashima

et al. 2009

Glia

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“…In this context, the functions of Klf10 and Klf11 have been studied in several cells that are TGF-beta-sensitive. Most of these studies have demonstrated that Klf10 and Klf11 mimic the effects of TGF-beta either in promoting apoptosis (Tachibana et al 1997;Ribeiro et al 1999;Bender et al 2004;Wang et al 2007;Jin et al 2007;Gohla et al 2008) or in decreasing proliferation (Cook et al 1998;Hefferan et al 2000b;Fernandez-Zapico et al 2003;Buck et al 2006). The pro-apoptotic effects of Klf10 and Klf11 seem to involve the transcriptional regulation of members of the Bcl-2 family.…”

Section: Role Of Klf10 and Klf11 In Apoptosis And Cell Cycle Progressionmentioning

confidence: 94%

Klf10 and Klf11 as mediators of TGF-beta superfamily signaling

Spittau

Krieglstein

2011

Cell Tissue Res

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Klf10 and Klf11 belong to the family of Sp1/Krüppel-like zinc finger transcription factors that play important roles in a variety of cell types and tissues. Although Klf10 and Klf11 were initially introduced as transforming growth factor-beta (TGF-beta)-inducible genes, several studies have described their upregulation by a plethora of growth factors, cytokines and hormones. Here, we review the current knowledge of the inductive cues for Klf10 and Klf11 and focus on their transcriptional regulation by members of the TGF-beta superfamily. We further summarize their involvement in the regulation of the TGF-beta signaling pathway and discuss their possible role as molecules mediating crosstalk between various signaling pathways. Finally, we provide an overview of the pro-apoptotic and anti-proliferative functions of Klf10 and Klf11.

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“…They have been also identified in rat, monkey, pig and zebrafish genomes [14], [22]. TIEG proteins are involved in numerous processes, including, among others, proliferation, apoptosis, differentiation, cancer and circadian rhythms [17], [23], [24], [25], [26], [27], [28], [29], [30]. These proteins can function as either transcriptional repressors [31], [32] or activators [32], [33], [34], [35], depending on the cellular context, the promoter to which they bind and the coregulators with which they interact [33], [34], [35].…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Activity and Nuclear Localization of Cabut, the Drosophila Ortholog of Vertebrate TGF-β-Inducible Early-Response Gene (TIEG) Proteins

et al. 2012

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BackgroundCabut (Cbt) is a C2H2-class zinc finger transcription factor involved in embryonic dorsal closure, epithelial regeneration and other developmental processes in Drosophila melanogaster. Cbt orthologs have been identified in other Drosophila species and insects as well as in vertebrates. Indeed, Cbt is the Drosophila ortholog of the group of vertebrate proteins encoded by the TGF-ß-inducible early-response genes (TIEGs), which belong to Sp1-like/Krüppel-like family of transcription factors. Several functional domains involved in transcriptional control and subcellular localization have been identified in the vertebrate TIEGs. However, little is known of whether these domains and functions are also conserved in the Cbt protein.Methodology/Principal FindingsTo determine the transcriptional regulatory activity of the Drosophila Cbt protein, we performed Gal4-based luciferase assays in S2 cells and showed that Cbt is a transcriptional repressor and able to regulate its own expression. Truncated forms of Cbt were then generated to identify its functional domains. This analysis revealed a sequence similar to the mSin3A-interacting repressor domain found in vertebrate TIEGs, although located in a different part of the Cbt protein. Using β-Galactosidase and eGFP fusion proteins, we also showed that Cbt contains the bipartite nuclear localization signal (NLS) previously identified in TIEG proteins, although it is non-functional in insect cells. Instead, a monopartite NLS, located at the amino terminus of the protein and conserved across insects, is functional in Drosophila S2 and Spodoptera exigua Sec301 cells. Last but not least, genetic interaction and immunohistochemical assays suggested that Cbt nuclear import is mediated by Importin-α2.Conclusions/SignificanceOur results constitute the first characterization of the molecular mechanisms of Cbt-mediated transcriptional control as well as of Cbt nuclear import, and demonstrate the existence of similarities and differences in both aspects of Cbt function between the insect and the vertebrate TIEG proteins.

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TIEG1 facilitates transforming growth factor‐β‐mediated apoptosis in the oligodendroglial cell line OLI‐neu

Cited by 33 publications

References 34 publications

Involvement of fractin in TGF‐β‐induced apoptosis in oligodendroglial progenitor cells

Involvement of fractin in TGF‐β‐induced apoptosis in oligodendroglial progenitor cells

Klf10 and Klf11 as mediators of TGF-beta superfamily signaling

Transcriptional Activity and Nuclear Localization of Cabut, the Drosophila Ortholog of Vertebrate TGF-β-Inducible Early-Response Gene (TIEG) Proteins

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