WT1 activates transcription of the splice factor kinase SRPK1 gene in PC3 and K562 cancer cells in the absence of corepressor BASP1

Belali, Tareg M.; Wodi, Chigeru; Clark, Bethany; Cheung, Man-Kim; Craig, Timothy; Wheway, Gabrielle; Wagner, Nicole; Wagner, Kay-Dietrich; Roberts, Stefan G. E.; Porazinski, Sean; Ladomery, Michael

doi:10.1016/j.bbagrm.2020.194642

Cited by 19 publications

(23 citation statements)

References 44 publications

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“…Our previous work has used K562 chronic myelogenous leukemia cells, which lack endogenous BASP1 but contain endogenous WT1. Stably introducing wtBASP1 into K562 cells (B-K562) represses WT1-dependent target genes compared to vector control K562 cells (V-K562; 7,11,12,16). We generated a K562 cell line derivative that expresses BASP1-Y12L (Y-K562), which, like wtBASP1, is largely nuclear (SI Appendix, Fig.…”

Section: Resultsmentioning

confidence: 99%

“…WT1 and BASP1 cooperate to drive transcriptional programs that control differentiation in several model cell line systems (7,11,12,(16)(17)(18). Recent studies in mice found that knockout of BASP1 in taste receptor cells leads to loss of differentiated phenotype and the reactivation of WT1 target genes that are normally associated with the progenitor cells (19).…”

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confidence: 99%

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Cholesterol is required for transcriptional repression by BASP1

Loats

Carrera

Fleming

et al. 2021

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

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Lipids are present within the cell nucleus, where they engage with factors involved in gene regulation. Cholesterol associates with chromatin in vivo and stimulates nucleosome packing in vitro, but its effects on specific transcriptional responses are not clear. Here, we show that the lipidated Wilms tumor 1 (WT1) transcriptional corepressor, brain acid soluble protein 1 (BASP1), interacts with cholesterol in the cell nucleus through a conserved cholesterol interaction motif. We demonstrate that BASP1 directly recruits cholesterol to the promoter region of WT1 target genes. Mutation of BASP1 to ablate its interaction with cholesterol or the treatment of cells with drugs that block cholesterol biosynthesis inhibits the transcriptional repressor function of BASP1. We find that the BASP1–cholesterol interaction is required for BASP1-dependent chromatin remodeling and the direction of transcription programs that control cell differentiation. Our study uncovers a mechanism for gene-specific targeting of cholesterol where it is required to mediate transcriptional repression.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Cholesterol is required for transcriptional repression by BASP1

Loats

Carrera

Fleming

et al. 2021

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

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“…The hypoxic conditions during development and after MI induced vascular formation via hypoxia-inducible factors, which directly upregulated Wt1 [ 49 , 75 ]. Wt1, in turn, regulates the expression of several angiogenic factors and receptors, positively [ 9 , 10 , 11 , 12 , 23 , 24 , 48 , 76 , 77 , 78 ]. De novo cardiomyocytes were reported to develop in adjacent areas of a myocardial infarction [ 79 , 80 ] and hypoxic regulation of Wt1 re-expression might also function to promote the tissue regeneration by cardiomyocytes differentiation from an activated progenitor pool [ 49 , 56 , 81 ].…”

Section: Discussionmentioning

confidence: 99%

“…Wt1 is an important regulator during embryogenesis [ 1 , 2 , 3 , 4 ] but is also involved in pathological processes, such as carcinogenesis. Originally proposed as a tumor suppressor, Wt1 is nowadays considered as an oncogene [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Wt1 is an evolutionary conserved transcription factor [ 13 ] with a high specificity for GC-rich regions [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Implications of the Wilms’ Tumor Suppressor Wt1 in Cardiomyocyte Differentiation

Wagner

Ninkov

Vukolic

et al. 2021

IJMS

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The Wilms’ tumor suppressor Wt1 is involved in multiple developmental processes and adult tissue homeostasis. The first phenotypes recognized in Wt1 knockout mice were developmental cardiac and kidney defects. Wt1 expression in the heart has been described in epicardial, endothelial, smooth muscle cells, and fibroblasts. Expression of Wt1 in cardiomyocytes has been suggested but remained a controversial issue, as well as the role of Wt1 in cardiomyocyte development and regeneration after injury. We determined cardiac Wt1 expression during embryonic development, in the adult, and after cardiac injury by quantitative RT-PCR and immunohistochemistry. As in vitro model, phenotypic cardiomyocyte differentiation, i.e., the appearance of rhythmically beating clones from mouse embryonic stem cells (mESCs) and associated changes in gene expression were analyzed. We detected Wt1 in cardiomyocytes from embryonic day (E10.5), the first time point investigated, until adult age. Cardiac Wt1 mRNA levels decreased during embryonic development. In the adult, Wt1 was reactivated in cardiomyocytes 48 h and 3 weeks following myocardial infarction. Wt1 mRNA levels were increased in differentiating mESCs. Overexpression of Wt1(-KTS) and Wt1(+KTS) isoforms in ES cells reduced the fraction of phenotypically cardiomyocyte differentiated clones, which was preceded by a temporary increase in c-kit expression in Wt1(-KTS) transfected ES cell clones and induction of some cardiomyocyte markers. Taken together, Wt1 shows a dynamic expression pattern during cardiomyocyte differentiation and overexpression in ES cells reduces their phenotypical cardiomyocyte differentiation.

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“…In particular, Belali et al showed that in PC3 cells, WT1 transcription factor is able to activate SRPK1 transcription and contributing to oncogenic processes through the activity of oncogenic splice factors such as SRSF1, and consequently by the expression of proangiogenic VEGF. 29 …”

Section: Discussionmentioning

confidence: 99%

SRSF‐1 and microvessel density immunohistochemical analysis by semi‐automated tissue microarray in prostate cancer patients with diabetes (DIAMOND study)

et al. 2021

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Objective: To study the association between insulin receptors (isoforms α and β), insulin growth factor-1 (IGF1) and serine/arginine splicing factor 1 (SRSF-1) in patients with prostate cancer (PC) and diabetes. Materials and Methods:We retrospectively analyzed data from 368 patients who underwent surgery for PC or benign prostatic hyperplasia (BPH) between 2010 and 2020 at the Department of Urology, University of Catania. Tissue microarray slides were constructed and they were stained for androgen receptor (AR), insulin receptor-α and -β, IGF1 (IGF1-R), Ki-67, and prostate specific membrane antigen (PSMA) expression using validated score. Results:The final cohort was represented by 100 patients with BPH and 268 with PC, with a median age of 68 years. We found that SRSF-1 expression was associated

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WT1 activates transcription of the splice factor kinase SRPK1 gene in PC3 and K562 cancer cells in the absence of corepressor BASP1

Cited by 19 publications

References 44 publications

Cholesterol is required for transcriptional repression by BASP1

Cholesterol is required for transcriptional repression by BASP1

Implications of the Wilms’ Tumor Suppressor Wt1 in Cardiomyocyte Differentiation

SRSF‐1 and microvessel density immunohistochemical analysis by semi‐automated tissue microarray in prostate cancer patients with diabetes (DIAMOND study)

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