The transcriptional repressor CTBP-1 functions in the nervous system of Caenorhabditis elegans to regulate lifespan

Reid, Anna; Yücel, Duygu; Wood, Mallory; Llamosas, Estelle; Kant, Sashi; Crossley, Merlin; Nicholas, Hannah R.

doi:10.1016/j.exger.2014.09.022

Cited by 11 publications

(16 citation statements)

References 49 publications

(71 reference statements)

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“…Additionally, others have shown that, in ctbp-1 mutants another pair of C. elegans neurons, the SMDDs, display late-onset morphological abnormalities coupled with a defect in C. elegans foraging behavior associated with these cells [54,55], indicating that CTBP-1 might act to maintain SMDD cell identity as well. The broad expression of ctbp-1 throughout much of the C. elegans nervous system is also consistent with the hypothesis that ctbp-1 functions broadly to maintain multiple neuronal cell identities [53].…”

Section: Ctbp-1 Likely Maintains the Identities Of Other Cells Besides That Of The Aiassupporting

confidence: 81%

“…The neuron-specific expression of ctbp-1 [53] suggests that CTBP-1 likely does not function in maintaining the identities of non-neuronal cells. How might non-neuronal cell identities be maintained?…”

Section: Transcriptional Corepressors Might Function Broadly In the Maintenance Of Cell Identitiesmentioning

confidence: 99%

“…Here we report the discovery that the C. elegans gene ctbp-1, which encodes the sole worm ortholog of the C-terminal Binding Protein (CtBP) family of transcriptional corepressors [47][48][49][50][51][52][53][54][55], functions to maintain the cell identity of the two AIA interneurons. We demonstrate that CTBP-1 functions with the SOXfamily transcription factor EGL-13 [56,57] to maintain multiple aspects of the AIA cell identity and propose that CTBP-1 does so in part by utilizing EGL-13 to repress transcriptional activity in the AIAs.…”

Section: Introductionmentioning

confidence: 99%

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The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in C. elegans

Saul

Hirose

Horvitz

2021

Preprint

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Cell identity is characterized by a distinct combination of gene expression, cell morphology and cellular function established as progenitor cells divide and differentiate. Following establishment, cell identities can be unstable and require active and continuous maintenance throughout the remaining life of a cell. Mechanisms underlying the maintenance of cell identities are incompletely understood. Here we show that the gene ctbp-1, which encodes the transcriptional corepressor C-terminal binding protein-1 (CTBP-1), is essential for the maintenance of the identities of the two AIA interneurons in the nematode Caenorhabditis elegans. ctbp-1 is not required for the establishment of the AIA cell fate but rather functions cell-autonomously and can act in older worms to maintain proper AIA gene expression, morphology and function. From a screen for suppressors of the ctbp-1 mutant phenotype, we identified the gene egl-13, which encodes a SOX family transcription factor. We found that egl-13 regulates AIA function and aspects of AIA gene expression, but not AIA morphology. We conclude that the CTBP-1 protein maintains AIA cell identity in part by utilizing EGL-13 to repress transcriptional activity in the AIAs. More generally, we propose that transcriptional corepressors like CTBP-1 might be critical factors in the maintenance of cell identities, harnessing the DNA-binding specificity of transcription factors like EGL-13 to selectively regulate gene expression in a cell-specific manner.

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Section: Ctbp-1 Likely Maintains the Identities Of Other Cells Besides That Of The Aiassupporting

confidence: 81%

Section: Transcriptional Corepressors Might Function Broadly In the Maintenance Of Cell Identitiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in C. elegans

Saul

Hirose

Horvitz

2021

Preprint

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“…Secondary antibody was α-guinea pig Alexa Fluor 488. V5 staining was performed with the V5 antibody (1:200; Novus Biologicals) and was performed as in Reid et al (2014) , with a few minor changes. Methanol fix after dissection was limited to 1 min, and acetone fix was removed.…”

Section: Methodsmentioning

confidence: 99%

Regulating chromosomal movement by the cochaperone FKB-6 ensures timely pairing and synapsis

Alleva

Balukoff

Peiper

et al. 2017

Journal of Cell Biology

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“… 6-8 Conversely, in Caenorhabditis elegans ( C. elegans) , inactivation of CtBP either by depletion or mutation resulted paradoxically in extended life span. 9,10 In addition to its role in developmental biology, transcriptional co-regulation by CtBP has been found to play a role in several diseases, including cancer. 11-14 CtBP promotes a neoplastic phenotype by suppressing tumor suppressor gene expression and by facilitating upregulation of oncogenic factors.…”

Section: Introductionmentioning

confidence: 99%

CtBP- an emerging oncogene and novel small molecule drug target: Advances in the understanding of its oncogenic action and identification of therapeutic inhibitors

Dcona

Morris

Ellis

et al. 2017

Cancer Biology & Therapy

103

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C-terminal Binding Proteins (CtBP) 1 and 2 are oncogenic transcriptional co-regulators overexpressed in many cancer types, with their expression level correlating to worse prognostic outcomes and aggressive tumor features. CtBP negatively regulates the expression of many tumor suppressor genes, while coactivating genes that promote proliferation, epithelial-mesenchymal transition, and cancer stem cell self-renewal activity. In light of this evidence, the development of novel inhibitors that mitigate CtBP function may provide clinically actionable therapeutic tools. This review article focuses on the progress made in understanding CtBP structure, role in tumor progression, and discovery and development of CtBP inhibitors that target CtBP's dehydrogenase activity and other functions, with a focus on the theory and rationale behind the designs of current inhibitors. We provide insight into the future development and use of rational combination therapy that may further augment the efficacy of CtBP inhibitors, specifically addressing metastasis and cancer stem cell populations within tumors.

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The transcriptional repressor CTBP-1 functions in the nervous system of Caenorhabditis elegans to regulate lifespan

Cited by 11 publications

References 49 publications

The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in C. elegans

The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in C. elegans

Regulating chromosomal movement by the cochaperone FKB-6 ensures timely pairing and synapsis

CtBP- an emerging oncogene and novel small molecule drug target: Advances in the understanding of its oncogenic action and identification of therapeutic inhibitors

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