The role of Elk-1 in gene regulation and cell survival
Başlık:
The role of Elk-1 in gene regulation and cell survival
Yazar:
Vickers, Elaine R., author.
ISBN:
9780438085350
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (202 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Özet:
The ETS-domain proteins constitute a large family of transcription factors. These are important in many cellular processes including development and tumourigenesis. Elk-1, a member of the TCF subfamily of ETS-proteins, is a point of convergence for MAPK pathways. These signalling cascades are central in the response of mammalian cells to mitogenic and stress stimuli. Activation of Elk-1 by MAPKs causes it to transcriptionally activate target genes, such as c-fos, in conjunction with a second transcription factor, SRF. Much is known regarding the way in which Elk-1 is activated, its ability to bind to DNA, and the mechanism by which it activates transcription of the c-fos gene. However, prior to this study no other definite target genes of Elk-1 had been identified, nor had its biological role been studied in a wider context. The fusion of a transcription factor to a potent transcriptional repression domain has been used in several instances to study transcription factor function. In this study, a dominant-negative form of Elk-1 was used to examine the phenotypic consequences of Elk-1 repression. It has now been shown that the silencing of Elk-1 responsive genes leads to cell cycle arrest, upregulation of the Cdk inhibitor p21cip1 and the induction of apoptotic cell death. Wild-type and constitutively active Elk-1 were found to be sufficient to rescue the cells from Elk-En-induced apoptosis. The specificity of this effect was verified using a mutant form of dominant-negative Elk-1, which is unable to interact with SRF. This mutant protein was unable to efficiently inhibit cell proliferation or induce apoptosis. Thus, SRF-dependent Elk-1 activity might play a role in cell survival. In order to identify Elk-1 target genes, a cDNA array approach was utilized. Several putative Elk-1 target genes have been identified including MCLl, a pro-survival target of MAPK cascades, and many other genes involved in cell-cycle regulation, signal transduction, cell-cell communication and transcriptional regulation. A number of possible SRF-independent targets of Elk-1 were also identified. Therefore, this study has suggested a novel role for the SRF-dependent activity of Elk-1 in driving cell cycle progression, promoting cell survival, and inhibiting apoptosis, as well as identifying many putative targets of Elk-1 mediated transcription.
Notlar:
School code: 1543
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(686953.1) | 686953-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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