RREB-1, a Novel Zinc Finger Protein, Is Involved in the Differentiation Response to Ras in Human Medullary Thyroid Carcinomas

Thiagalingam, Arunthathi; Bustros, A de; Borges, Michael; Jasti, Ravirasmi; Compton, Debra L; Diamond, Lisa E.; Mabry, Mack; Ball, Douglas W.; Baylin, Stephen B.; Nelkin, Barry D.

doi:10.1128/mcb.16.10.5335

Cited by 136 publications

(145 citation statements)

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“…Despite its implication in Ras, Ral, p16, p53, and androgen receptor 10,11,14,19,20 signaling pathways, sparse data exist regarding the nature, expression, or function of RREB1 mRNA and protein in cancer cells. This is the first study to address this gap by describing RREB1 expression in human cancers, as well as the first to examine isoform expression in human tissues and cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…10 The significance of RREB1 continues to be elucidated as studies have found it to function in either the induction or repression of gene expression. Genes induced by RREB1 include those encoding calcitonin, 11 FSH, 12 MT-IIA, 13 p53, 14 and secretin 15 ; genes repressed by RREB1 include those encoding angiotensinogen, 16 HLA-G, 17 hZIP1, 18 p16, 19 and PSA. 20 RREB1 has also been found to bind nuclear proteins, such as CtBP, 21 NeuroD, 15 and androgen receptor (AR).…”

mentioning

confidence: 99%

“…20 The initial study of RREB1 found that the gene product bound the calcitonin promoter in medullary thyroid carcinomas in response to Ras. 11 In bladder cancer, the tumor suppressor p16 is commonly lost as an early event in tumorigenesis, and RREB1 was found to bind and repress transcription of the Cdkn2a locus. 19 Depletion of RREB1 by siRNA slows cell migration and cell spreading in breast cell lines, 22 whereas in breast cancer and osteosarcoma cells RREB1 binds the p53 promoter and transactivates p53 expression on DNA damage.…”

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confidence: 99%

“…16 It was initially described as a 755-amino-acid C 2 H 2 zinc finger protein (RREB-1), 11 although subsequent analyses in chicken and human cells indicated that RREB1 encodes a longer protein of 1656 (Finb) amino acids (AA) in humans. 13,31 A second variant encoding 1397 amino acids ] with a unique C-terminus was also identified.…”

mentioning

confidence: 99%

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RREB1 Transcription Factor Splice Variants in Urologic Cancer

Nitz

Harding

Smith

et al. 2011

The American Journal of Pathology

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RREB1 is an alternatively spliced transcription factor implicated in Ras signaling and cancer. Little is known about the expression of RREB1 isoforms in cell lines or human tumors, or about the clinical relevance of the latter. We have developed tools for IHC of RREB1 protein isoform-specific amplification of RREB1 mRNA and selective knockdown of RREB1 isoforms and use these to provide new information by characterizing RREB1 expression in bladder and prostate cancer cell lines and human tissue samples. Previously described splice variants RREB1␣, RREB1␤, RREB1␥, and RREB1␦ were identified, as well as the novel variant RREB1 . Total and isoform-specific mRNA expression was lower in most but not all tumors, compared with normal tissues. RREB1 IHC performed on a bladder cancer TMA did not indicate a relationship between total RREB1 expression and overall survival after radical cystectomy for invasive bladder cancer. In contrast, in vitro proliferation studies using the UMUC-3 bladder cancer cell line after selective isoform-specific knockdown of expression indicate that RREB1␣ is not necessary for proliferation, but that RREB1␤ may be required. These contributions should accelerate progress in the nascent RREB1 field by providing new reagents while also providing clues to the role of RREB1 isoforms in human cancer and raising the possibility of isoform-specific roles in human carcinogenesis and progression.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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RREB1 Transcription Factor Splice Variants in Urologic Cancer

Nitz

Harding

Smith

et al. 2011

The American Journal of Pathology

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“…CARRIE also predicted that the Ras-responsive element-binding protein (RREB)-1 is regulated by the Ral GTPases. RREB-1 was discovered as a zinc-finger protein involved in mediating a Ras-driven differentiation program in a thyroid carcinoma cell line (Thiagalingam et al, 1996). Given that both Ral and RREB-1 are regulated by Ras, we sought to determine the accuracy of the CARRIE prediction.…”

Section: Rala and Ralb Signal Via Different Repertoires Of Transcriptmentioning

confidence: 99%

Expression profiling of Ral-depleted bladder cancer cells identifies RREB-1 as a novel transcriptional Ral effector

2007

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Although the monomeric GTPases RalA and RalB have been shown to regulate a variety of transcription factors, little is known regarding the differences or similarities in transcriptional programs regulated by RalA compared to RalB. Further, the association of these transcriptional pathways to human carcinogenesis and progression remains unclear. Here, we studied the role of RalA and/ or RalB in transcriptional regulation by combining short interfering RNA depletion of Ral with gene expression profiling via microarray in the human bladder cancer cell line, UMUC-3. A large number of genes were found to be similarly modulated in cells with RalA and RalB depletion, suggesting that RalA and RalB impinge on overlapping transcriptional signaling pathways. However, smaller sets of genes were modulated by depletion of RalA or RalB, indicating that these closely related proteins also regulate nonoverlapping transcriptional pathways. Computational analysis of upstream sequences of genes modulated by Ral depletion identified Ras-responsive element-binding protein (RREB)-1, as a putative Ral transcriptional target, which we verified experimentally. Importantly, as a group, Ral-regulated probe sets identified here were disproportionally represented among those differentially expressed as a function of human bladder transformation. Taken together, these data strongly suggest that Ral family members mediate both common and specific transcriptional programs that are associated with human cancer and identify RREB-1 as a novel transcriptional effector of Ral.

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Hindsight regulates photoreceptor axon targeting through transcriptional control of jitterbug/Filamin and multiple genes involved in axon guidance in Drosophila

Oliva

Molina-Fernandez

Maureira

et al. 2015

Developmental Neurobiology

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During axon targeting, a stereotyped pattern of connectivity is achieved by the integration of intrinsic genetic programs and the response to extrinsic long and short-range directional cues. How this coordination occurs is the subject of intense study. Transcription factors play a central role due to their ability to regulate the expression of multiple genes required to sense and respond to these cues during development. Here we show that the transcription factor HNT regulates layer-specific photoreceptor axon targeting in Drosophila through transcriptional control of jbug/Filamin and multiple genes involved in axon guidance and cytoskeleton organization.Using a microarray analysis we identified 235 genes whose expression levels were changed by HNT overexpression in the eye primordia. We analyzed nine candidate genes involved in cytoskeleton regulation and axon guidance, six of which displayed significantly altered gene expression levels in hnt mutant retinas. Functional analysis confirmed the role of OTK/PTK7 in photoreceptor axon targeting and uncovered Tiggrin, an integrin ligand, and Jbug/Filamin, a conserved actin- binding protein, as new factors that participate of photoreceptor axon targeting. Moreover, we provided in silico and molecular evidence that supports jbug/Filamin as a direct transcriptional target of HNT and that HNT acts partially through Jbug/Filamin in vivo to regulate axon guidance. Our work broadens the understanding of how HNT regulates the coordinated expression of a group of genes to achieve the correct connectivity pattern in the Drosophila visual system. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1018-1032, 2015.

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RREB-1, a Novel Zinc Finger Protein, Is Involved in the Differentiation Response to Ras in Human Medullary Thyroid Carcinomas

Cited by 136 publications

References 53 publications

RREB1 Transcription Factor Splice Variants in Urologic Cancer

RREB1 Transcription Factor Splice Variants in Urologic Cancer

Expression profiling of Ral-depleted bladder cancer cells identifies RREB-1 as a novel transcriptional Ral effector

Hindsight regulates photoreceptor axon targeting through transcriptional control of jitterbug/Filamin and multiple genes involved in axon guidance in Drosophila

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