The Wilms Tumor Suppressor WT1 Encodes a Transcriptional Activator of amphiregulin

  title={The Wilms Tumor Suppressor WT1 Encodes a Transcriptional Activator of amphiregulin},
  author={Sean-Bong Lee and Karen Huang and Rachel E. Palmer and Vivi B Truong and Doris A. Herzlinger and Kathryn Ann Kolquist and Jenise C Wong and Charles Paulding and Seung Kew Yoon and William L. Gerald and Jonathan Daniel Oliner and Daniel A. Haber},

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Identification of Connective Tissue Growth Factor as a Target of WT1 Transcriptional Regulation*
The results indicate that CTGF is a bona fide target of WT1 transcriptional suppression and likely plays a role in Wilms tumorigenesis and associated disease syndromes.
The tumor suppressor WTX shuttles to the nucleus and modulates WT1 activity
It is reported that WTX translocates to the nucleus, a property that is modified by an endogenous splicing variant and is modulated by a nuclear export inhibitor, suggesting a role for WTX in nuclear pathways implicated in the transcriptional regulation of cellular differentiation programs.
A Functional Interaction with CBP Contributes to Transcriptional Activation by the Wilms Tumor Suppressor WT1*
It is reported here that WT1 binds to the transcriptional coactivator CBP, leading to synergistic activation of a physiologically relevant promoter, which supports a model of WT1 as a transcriptional activator of genes required for cellular differentiation.
Mechanisms of transcriptional regulation by WT1 (Wilms' tumour 1).
The wealth of the growing molecular information that defines the current understanding of the versatility and utility of WT1 as a master regulator of organ development, a tumour suppressor and an oncogene is discussed.
Identification of Novel Wilms' Tumor Suppressor Gene Target Genes Implicated in Kidney Development*
A genome-wide screen implicates WT1 in the transcriptional regulation of the EGF-family of growth factors as well as the CX3CL1 chemokine during nephrogenesis.
BASP1 Is a Transcriptional Cosuppressor for the Wilms' Tumor Suppressor Protein WT1
BASP1 is a WT1-associated factor that can regulate WT1 transcriptional activity and is presented as direct evidence that this requires a transcriptional cosuppressor.
hnRNP-U directly interacts with WT1 and modulates WT1 transcriptional activation
It is shown that endogenous WT1 binds to heterogeneous nuclear ribonuclear protein U (hnR NP-U), that this interaction does not require any other proteins or nucleic acids, and that hnRNP-U can modulate WT1 transcriptional activation of a bona fide WT1 target gene.
Anlaysis of complementary expression profiles following WT1 induction versus repression reveals the cholesterol/fatty acid synthetic pathways as a possible major target of WT1
Evidence is provided that the C-terminal end of the WT1 protein can directly interact with SREBP, suggesting that WT1 may modify the transcriptional function of SREBPs via a direct protein–protein interaction.
The Wilms tumor suppressor WT1 regulates early gonad development by activation of Sf1.
It is demonstrated here that WT1 and LHX9 function as direct activators of the Sf1 gene, and a pathway in which the products of the Wt1 and Lhx9 genes activate expression of S f1 and thus mediate early gonadogenesis is suggested.
WT1 induces apoptosis through transcriptional regulation of the proapoptotic Bcl-2 family member Bak.
The hypothesis that Wilms' tumors arise, in part, because WT1 mutant proteins fail to promote programmed cell death during kidney development is supported.


Tumor-associated WT1 Missense Mutants Indicate That Transcriptional Activation by WT1 Is Critical for Growth Control*
It is found that three N-terminal tumor-associated missense mutations of WT1 were defective for activation of both a synthetic reporter containing WT1-binding sites as well as the promoter of a WT1 responsive gene, p21.
Induction of p21 by the Wilms' tumor suppressor gene WT1.
It is shown that WT1-mediated apoptosis is preceded by induction of the cyclin-dependent kinase inhibitor p21, associated with G1 phase arrest, and this effect is only demonstrated by WT1 isoforms with an intact DNA binding domain, and it is associated with increased expression of endogenous p21 mRNA.
WT1 suppresses synthesis of the epidermal growth factor receptor and induces apoptosis.
Repression of EGFR and induction of apoptosis by mechanism that may contribute to its critical role in normal kidney development and to the immortalization of tumor cells with inactivated WT1 alleles are studied.
The WT1 Wilms tumor gene product: a developmentally regulated transcription factor in the kidney that functions as a tumor suppressor.
  • F. Rauscher
  • Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1993
The role of WT1 in normal kidney development processes, the known biochemical functions of the protein and the status of identifying target genes regulated by this potentially oncogenic transcription factor are reviewed.
WT1-mediated growth suppression of Wilms tumor cells expressing a WT1 splicing variant.
A human Wilms tumor cell line (RM1) was developed to test the tumor suppressor activity of WT1, a zinc finger transcription factor that is expressed in the developing human kidney and is mutationally
Inhibition of cellular proliferation by the Wilms tumor suppressor WT1 requires association with the inducible chaperone Hsp70.
Observations indicate that Hsp70 is an important cofactor for the function of WT1, and suggest a potential role for this chaperone during kidney differentiation.
The Wilms’ Tumor Suppressor Gene (wt1) Product Regulates Dax-1 Gene Expression during Gonadal Differentiation
The results indicate that the WT1–DAX-1 pathway is an early event in the process of mammalian sex determination, and it is suggested that WT1 regulates Dax-1via GC-rich binding sites found upstream of the DX1 TATA box.
WAF1, a potential mediator of p53 tumor suppression
The amphiregulin gene encodes a novel epidermal growth factor-related protein with tumor-inhibitory activity.
Human placenta and ovaries were found to express significant amounts of the 1.4-kilobase AR transcript, implicating AR in the regulation of normal cell growth, and the gene was localized to chromosomal region 4q13-4q21, a common breakpoint for acute lymphoblastic leukemia.