ETS-Domain Transcription Factor Elk-1 Regulates Stemness Genes in Brain Tumors and CD133+ BrainTumor-Initiating Cells

Söğüt, Melis Savaşan; Venugopal, Chitra; Kandemir, B.; Dağ, Uğur; Mahendram, Sujeivan; Singh, Sheila K.; Gulfidan, Gizem; Arğa, Kazım Yalçın; Yılmaz, Bayram; Kurnaz, Işıl Aksan

doi:10.3390/jpm11020125

Cited by 10 publications

(8 citation statements)

References 44 publications

(54 reference statements)

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“…ELK-1 KD decreased SOX2 in western blots from tectum and increased neural progenitor cell apoptosis, consistent with the observation that ELK-1 KD decreases expression of 'stemness' genes, such as sox2, oct4, nanog (Sogut et al, 2021). These studies suggest that ELK-1 KD drives neural progenitor cells to expand the progenitor pool through symmetric divisions, while also increasing neural progenitor cell apoptosis.…”

Section: Brca1 and Elk-1 Knockdown Occlude The Effects Of Visual Experience On Neural Progenitor Cell Fatesupporting

confidence: 84%

“…In addition, BRCA1 and ELK-1 interact and this interaction enhances BRCA1 function, suggesting that ELK-1 may function downstream of BRCA1 (Chai et al, 2001). Decreased levels of BRCA1 and ELK-1 in the tectum increased neural progenitor cell apoptosis, consistent with the observation that ELK-1 KD decreases expression of 'stemness' genes, such as sox2, oct4, nanog (Sogut et al, 2021). These studies suggest that BRCA1 KD and ELK-1 KD drive neural progenitor cells to expand the progenitor pool through symmetric divisions, while also increasing neural progenitor cell apoptosis.…”

Section: Brca1 and Elk-1 Knockdown Occlude The Effects Of Visual Experience On Neural Progenitor Cell Fatesupporting

confidence: 75%

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BRCA1 and ELK-1 regulate Neural Progenitor Cell Fate in the Optic Tectum in response to Visual Experience in Xenopus laevis tadpoles

Huang

et al. 2021

Preprint

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In developing Xenopus tadpoles, the optic tectum begins to receive patterned visual input while visuomotor circuits are still undergoing neurogenesis and circuit assembly. This visual input regulates neural progenitor cell fate decisions such that maintaining tadpoles in the dark increases proliferation, expanding the progenitor pool, while visual stimulation promotes neuronal differentiation. To identify regulators of activity-dependent neural progenitor cell fate, we used RNA-Seq to profile the transcriptomes of proliferating neural progenitor cells and newly-differentiated immature neurons. Out of 1,130 differentially expressed (DE) transcripts, we identified six DE transcription factors which are predicted to regulate the majority of the other DE transcripts. Here we focused on Breast cancer 1 (BRCA1) and the ETS-family transcription factor, ELK-1. BRCA1 is known for its role in cancers, but relatively little is known about its potential role in regulating neural progenitor cell fate. ELK-1 is a multifunctional transcription factor which regulates immediate early gene expression. We investigated the effect of BRCA1 and ELK-1 on activity-regulated neurogenesis in the tadpole visual system using in vivo timelapse imaging to monitor the fate of turbo-GFP-expressing SOX2+ neural progenitor cells in the optic tectum. Our longitudinal in vivo imaging analysis shows that knockdown of either BRCA1 or ELK-1 altered the fates of neural progenitor cells, and furthermore that the effects of visual experience on neurogenesis depend on BRCA1 expression, while the effects of visual experience on neuronal differentiation depend on ELK-1 expression. These studies provide insight into the potential mechanisms by which neural activity affects neural progenitor cell fate.

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Section: Brca1 and Elk-1 Knockdown Occlude The Effects Of Visual Experience On Neural Progenitor Cell Fatesupporting

confidence: 84%

Section: Brca1 and Elk-1 Knockdown Occlude The Effects Of Visual Experience On Neural Progenitor Cell Fatesupporting

confidence: 75%

BRCA1 and ELK-1 regulate Neural Progenitor Cell Fate in the Optic Tectum in response to Visual Experience in Xenopus laevis tadpoles

Huang

et al. 2021

Preprint

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“…The protein-protein interaction (PPI) network of Elk-1 in mitotic kinase phosphoproteomes, we have initially integrated human whole PPI network with our previously reported microarray results from SH-SY5Y cells overexpressing constitutively active Elk-1VP16 fusion protein ( Figure 5(a) ; Suppl. Table 2 ) [ 26 ]. The resulting Elk-1-specific PPI network was further filtered with the mitotic phosphoproteomes, which include proteins in G1 phase, M phase, G1&M phase, and noncell cycle proteins, and with the two phosphoproteome sets reported previously for Aurora kinase and Aurora/Plk kinases ( Figure 5 ) [ 21 , 22 ].…”

Section: Resultsmentioning

confidence: 99%

Mitotic Kinases Aurora-A, Plk1, and Cdk1 Interact with Elk-1 Transcription Factor through the N-Terminal Domain

Uyar,

Babal,

Yılmaz

et al. 2024

International Journal of Cell Biology

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Elk-1 is a member of the ETS domain transcription factor superfamily that is phosphorylated upon mitogen-activated protein kinase (MAPK) pathway activation, which in turn regulated its interaction with partner protein serum response factor (SRF), leading to formation of a ternary complex with DNA. It has previously been reported that Elk-1 interacts with a mitotic kinase Aurora-A, although the mechanisms or the relevance of this interaction was unclear. Elk-1 was also reported to be phosphorylated by CDK5 on Thr417 residue. In this study, we show for the first time that this transcription factor interacts not only with Aurora-A but also with other mitotic kinases Aurora-B, Plk1, and Cdk1, and we define the interaction domain on Elk-1 to the first N-terminal 205 amino acids. We also describe putative phosphorylation sites of these mitotic kinases on Elk-1 and show that Elk-1 peptides containing these residues get phosphorylated by the mitotic kinases in in vitro kinase assays. We also perform bioinformatic analysis of mitotic phosphoproteomes and determine potential interaction partners for Elk-1 in Plk or Aurora phosphoproteomes. We propose that understanding the dynamic phosphorylation of Elk-1 by mitotic kinases is important and that it can present a novel target for anticancer strategies.

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“…2 ), the observation that BRCA1 and ELK-1 interact with each other in a network of candidate master regulators and regulate a total of 270 target genes ( Fig. 3 and SI Appendix , Table S2 ) and the relative paucity of information about their roles in NPCs ( 20 – 23 ).…”

Section: Resultsmentioning

confidence: 99%

BRCA1 and ELK-1 regulate neural progenitor cell fate in the optic tectum in response to visual experience in Xenopus laevis tadpoles

Huang,

McKeown,

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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In developing Xenopus tadpoles, the optic tectum begins to receive patterned visual input while visuomotor circuits are still undergoing neurogenesis and circuit assembly. This visual input regulates neural progenitor cell fate decisions such that maintaining tadpoles in the dark increases proliferation, expanding the progenitor pool, while visual stimulation promotes neuronal differentiation. To identify regulators of activity-dependent neural progenitor cell fate, we profiled the transcriptomes of proliferating neural progenitor cells and newly differentiated neurons using RNA-Seq. We used advanced bioinformatic analysis of 1,130 differentially expressed transcripts to identify six differentially regulated transcriptional regulators, including Breast Cancer 1 (BRCA1) and the ETS-family transcription factor, ELK-1, which are predicted to regulate the majority of the other differentially expressed transcripts. BRCA1 is known for its role in cancers, but relatively little is known about its potential role in regulating neural progenitor cell fate. ELK-1 is a multifunctional transcription factor which regulates immediate early gene expression. We investigated the potential functions of BRCA1 and ELK-1 in activity-regulated neurogenesis in the tadpole visual system using in vivo time-lapse imaging to monitor the fate of GFP-expressing SOX2+ neural progenitor cells in the optic tectum. Our longitudinal in vivo imaging analysis showed that knockdown of either BRCA1 or ELK-1 altered the fates of neural progenitor cells and furthermore that the effects of visual experience on neurogenesis depend on BRCA1 and ELK-1 expression. These studies provide insight into the potential mechanisms by which neural activity affects neural progenitor cell fate.

show abstract

ETS-Domain Transcription Factor Elk-1 Regulates Stemness Genes in Brain Tumors and CD133+ BrainTumor-Initiating Cells

Cited by 10 publications

References 44 publications

BRCA1 and ELK-1 regulate Neural Progenitor Cell Fate in the Optic Tectum in response to Visual Experience in Xenopus laevis tadpoles

BRCA1 and ELK-1 regulate Neural Progenitor Cell Fate in the Optic Tectum in response to Visual Experience in Xenopus laevis tadpoles

Mitotic Kinases Aurora-A, Plk1, and Cdk1 Interact with Elk-1 Transcription Factor through the N-Terminal Domain

BRCA1 and ELK-1 regulate neural progenitor cell fate in the optic tectum in response to visual experience in Xenopus laevis tadpoles

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