A role of WT1 in cell division and genomic stability

Shandilya, Jayasha; Roberts, Stefan G. E.

doi:10.1080/15384101.2015.1021525

Cited by 25 publications

(19 citation statements)

References 64 publications

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“…The Wilms’ tumor 1 gene product, which can either be tumor suppressive (146) or oncogenic (147–151), can regulate h TERT gene expression and hence telomerase activity in cancer cells via multiple pathways (12; Fig. 3).…”

Section: Ets1 and Ets2mentioning

confidence: 99%

Aberrant expression of ETS1 and ETS2 proteins in cancer

Fry

Inoue

2018

Cancer Rep Rev

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The ETS transcription factors regulate expression of genes involved in normal cell development, proliferation, differentiation, angiogenesis, and apoptosis, consisting of 28 family members in humans. Dysregulation of these transcription factors facilitates cell proliferation in cancers, and several members participate in invasion and metastasis by activating gene transcription. ETS1 and ETS2 are the founding members of the ETS family and regulate transcription by binding to ETS sequences. They are both involved in oncogenesis and tumor suppression depending on the biological situations used. The essential roles of ETS proteins in human telomere maintenance have been suggested, which have been linked to creation of new Ets binding sites. Recently, preferential binding of ETS2 to gain-of-function mutant p53 and ETS1 to wild type p53 (WTp53) has been suggested, raising the tumor promoting role for the former and tumor suppressive role for the latter. The oncogenic and tumor suppressive functions of ETS1 and 2 proteins have been discussed.

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Section: Ets1 and Ets2mentioning

confidence: 99%

Aberrant expression of ETS1 and ETS2 proteins in cancer

Fry

Inoue

2018

Cancer Rep Rev

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“…Mutations in WT1 gene have been implicated in abnormal development of the genito-urinary system resulting in syndromes such as Wilm's Tumor, Denys-Drash, WAGR and Frasier [4][5][6][7][8]. Recent studies however suggest an even wider spectrum of functions for WT1, including epigenetic regulation of genes [9][10][11][12], stem cell differentiation [13] and genome stability [14,15].…”

Section: Introductionmentioning

confidence: 99%

Structure of WT1 zinc fingers bound to its cognate DNA: Implications of the KTS insert

Yengo

Nurmemmedov

Thunnissen

2018

Preprint

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WT1 is a transcription factor with a DNA binding N-terminal domain containing four C2H2-type zinc fingers. In order to perform its role as a transcription factor, WT1 needs to specifically recognize and properly bind to its target DNA. How this is done is still not completely clear. Two of WT1's major isoforms are distinguished by the presence or absence of a 3 amino acid insert, Lysine-Threonine-Serine (KTS) in the linker between zinc-fingers 3 and 4. This KTS insert is conserved throughout all life forms expressing WT1. The -KTS isoform, which acts as a transcription factor, binds DNA with higher affinity than the +KTS isoform, which is thought to participate in RNA splicing and interaction with partner proteins. This study was aims at elucidating the effect of the KTS insert on DNA binding. Here we present the crystal structure of WT1 zinc fingers 2-4, with and without the KTS insert, bound to the WT1 9-base pair cognate DNA sequence, refined to 1.9 Å and 2.5 Å respectively. The structures show that the +KTS isoform of WT1 recognizes DNA with the same specificity as the -KTS isoform. The only differences in the DNA bound conformation of the two isoforms are found within the linker containing the KTS, and these mainly involve the loss of the C-capping interactions thought to stabilize the complex. These structures provide the molecular detail necessary for the interpretation of the WT1 transcriptional DNA recognition and validation of its transcriptional targets.

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“…After DNA replication, programmed double-stranded breaks (DSBs) formation is catalysed by Spo11 (Rec12 in S. pombe) which subsequently initialises homologous recombination and crossing over (Sharif, 2002). This physical connection of homologous chromosomes, together with sister chromatid cohesion, is required for correct microtubule -kinetochore interaction, in the way that homologous chromosomes are connected to microtubules emanating from opposite spindle poles (Murata-Hori, and Wang, 2002).…”

Section: Meiosis In S Pombementioning

confidence: 99%

“…This physical connection of homologous chromosomes, together with sister chromatid cohesion, is required for correct microtubule -kinetochore interaction, in the way that homologous chromosomes are connected to microtubules emanating from opposite spindle poles (Murata-Hori, and Wang, 2002). As a control mechanism, the spindle assembly checkpoint prevents metaphase/anaphase transition, until all homologous chromosomes biorient on the meiosis I spindle (Shandilya, Roberts 2015). Another important feature required for proper alignment of chromosomes on the spindle is sister chromatid cohesion.…”

Section: Meiosis In S Pombementioning

confidence: 99%