The Transcription Factor Spi-1/PU.1 Interacts with the Potential Splicing Factor TLS

Hallier, Marc; Lerga, Ana; Barnache, Stéphane; Tavitian, Armand; Moreau-Gachelin, Françoise

doi:10.1074/jbc.273.9.4838

Cited by 125 publications

(141 citation statements)

References 19 publications

Supporting

Mentioning

136

Contrasting

Unclassified

Order By: Relevance

“…Spi-1/PU.1 is an Ets protein that binds DNA (Klemsz et al, 1990) and RNA (Hallier et al, 1998). Spi-1/PU.1 plays an essential role in normal lymphopoiesis and myelopoiesis.…”

Section: Introductionmentioning

confidence: 99%

Spi-1 transgenic mice develop a clonal erythroleukemia which does not depend on p53 mutation

et al. 1998

Self Cite

View full text Add to dashboard Cite

Spi-1 transcriptional activation and wild-type p53 extinction are two oncogenic alterations involved in the malignant transformation of erythroblasts during the Friend acute erythroleukemia. To dissect the contribution of these alterations in the deregulation of the di erentiation and proliferation of erythroblasts, we generated spi-1 transgenic mice. Analysis of these animals revealed that Spi-1 overexpression was directly involved in the block of proerythroblast di erentiation. However, the erythroleukemia that develops in these animals evolved in two steps. During the early step (HS1 step), non tumorigenic proerythroblasts remained strictly dependent upon erythropoietin (Epo) for their survival and proliferation. Later on, Epo-independent and tumorigenic proerythroblasts emerged (HS2 step) suggesting that other oncogenes cooperate with Spi-1 to lead to a fully malignant phenotype. By provirus tagging, we demonstrate that the HS1 step was clonal indicating that a cell selection must occur in vivo. Analysis of the nature of p53 in both the in vivo HS1 and HS2 proerythroblasts and in cultured erythroblastic cell lines showed that ± p53 was normal in the HS1 primary tissues but was mutated in the HS1 cultured cell lines ± p53 was frequently altered in HS2 primary tissues but was found normal in some mice. These data indicate that (i) the blockage of the erythroblast di erentiation by Spi-1 occurs independently of p53 alteration (ii) p53 alteration is not necessary to confer Epo independence and tumorigenicity to spi-1 transgenic proerythroblasts.

show abstract

“…Spi-1/PU.1 is an Ets protein that binds DNA (Klemsz et al, 1990) and RNA (Hallier et al, 1998). Spi-1/PU.1 plays an essential role in normal lymphopoiesis and myelopoiesis.…”

Section: Introductionmentioning

confidence: 99%

Spi-1 transgenic mice develop a clonal erythroleukemia which does not depend on p53 mutation

et al. 1998

Self Cite

View full text Add to dashboard Cite

show abstract

“…NonO has signi®cant homology with PSF over a 320aa region, encompassing the RNA binding domains (Dong et al, 1993). This striking degree of homology suggested that NonO was also a splicing factor and indeed it has been shown that its depletion from nuclear extract inhibits b-globin splicing in vitro (Hallier et al, 1998). NonO may have a role in transcriptional activation (Basu et al, 1997) and was also shown to bind PU.1 an ETS family protein that can alter the splicing activity of NonO in vitro (Hallier et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

PRCC, the commonest TFE3 fusion partner in papillary renal carcinoma is associated with pre-mRNA splicing factors

et al. 2001

View full text Add to dashboard Cite

In papillary renal cell carcinomas the TFE3 transcription factor becomes fused to the PSF and NonO pre-mRNA splicing factors and most commonly to a protein of unknown function designated PRCC. In this study we have examined the ability of the resulting PRCC ± TFE3 and NonO ± TFE3 fusions to activate transcription from the plasminogen activator inhibitor-1 (PAI-1) promoter. The results show that only fusion to PRCC enhanced transcriptional activation, indicating that the ability to enhance the level of transcription from endogenous TFE3 promoters is not a consistent feature of TFE3 fusions. In investigations of the normal function of PRCC we observed that PRCC expressed as a green¯uorescent fusion protein colocalizes within the nucleus with Sm premRNA splicing factors. It was also found that endogenous PRCC is coimmunoprecipitated by antibodies that recognize a variety of pre-mRNA splicing factors including SC35, PRL1 and CDC5. Association with the cellular splicing machinery is therefore, a common feature of the proteins that become fused to TFE3 in papillary renal cell carcinomas. Oncogene (2001) 20, 178 ± 187.

show abstract

“…26). All other antibodies in this study were from Santa Cruz Biotechnology, Inc., and include mouse monoclonal anti-Cdk1 (clone 17, 1: 200 dilution), anti-Cdk2 (D-12, 1:200 dilution), and anti -h-actin (AC15, 1:1,000 dilution).…”

Section: Antibodies and Western Blottingmentioning

confidence: 99%

TLS-ERG Leukemia Fusion Protein Deregulates Cyclin-Dependent Kinase 1 and Blocks Terminal Differentiation of Myeloid Progenitor Cells

Pan

Zou

Wu³

et al. 2008

Molecular Cancer Research

View full text Add to dashboard Cite

TLS-ERG fusion protein is derived from the t(16;21) translocation found in human myeloid leukemia. Here, we show that retroviral transduction of TLS-ERG confers a growth advantage to L-G myeloid progenitor cells and blocks terminal differentiation. We found that the level of cyclin-dependent kinase 1 (Cdk1) protein was significantly decreased in controls but unchanged in TLS-ERG -expressing cells after granulocyte colony-stimulating factor treatment or interleukin-3 withdrawal. Injection of TLS-ERG -expressing L-G cells induced rapid development of a leukemia-like disease in syngeneic mice. Through site-directed mutagenesis, we showed that transformation and deregulation of Cdk1 by TLS-ERG require an intact ets DNA-binding domain within the fusion protein. Interestingly, treatment of TLS-ERG -expressing L-G cells with 5-aza-2 ¶-deoxycytidine (Decitabine) or trichostatin A resulted in down-regulation of Cdk1 and induction of terminal differentiation. To investigate whether Cdk1 deregulation is indeed responsible for transformation by TLS-ERG, we constructed lentiviral vectors for delivery of Cdk1 mutants and small interfering RNA (siRNA). Both dominant-negative inhibition and siRNA knockdown of Cdk1 were able to restore the ability of TLS-ERG -expressing L-G cells to undergo terminal differentiation. In addition, siRNA knockdown of Cdk1 in YNH-1 cells derived from a t(16;21) acute myelogenous leukemia patient also resulted in terminal differentiation. As restoration of terminal myeloid differentiation to TLS-ERG cells is dependent on cell cycle arrest, our findings suggest an important role for Cdk1 in cellular transformation and may be useful in the search for new treatments of TLS-ERG -associated myeloid leukemia. (Mol Cancer Res 2008;6(5):862 -72)

show abstract

The Transcription Factor Spi-1/PU.1 Interacts with the Potential Splicing Factor TLS

Cited by 125 publications

References 19 publications

Spi-1 transgenic mice develop a clonal erythroleukemia which does not depend on p53 mutation

Spi-1 transgenic mice develop a clonal erythroleukemia which does not depend on p53 mutation

PRCC, the commonest TFE3 fusion partner in papillary renal carcinoma is associated with pre-mRNA splicing factors

TLS-ERG Leukemia Fusion Protein Deregulates Cyclin-Dependent Kinase 1 and Blocks Terminal Differentiation of Myeloid Progenitor Cells

Contact Info

Product

Resources

About