Human wig-1, a p53 target gene that encodes a growth inhibitory zinc finger protein

Hellborg, Fredrik; Wang, Qian; Méndez-Vidal, Cristina; Asker, Charlotte; Kost‐Alimova, Maria; Wilhelm, Margareta; Imreh, Stefan; Wiman, Klas G.

doi:10.1038/sj.onc.1204722

Cited by 58 publications

(63 citation statements)

References 33 publications

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“…6C). Activation of Ak1 and Wig1 by p53 can inhibit cellular proliferation (29,32,33). Our data suggest that these factors may also play important roles in p53 tumor suppression.…”

Section: Resultsmentioning

confidence: 75%

p21 delays tumor onset by preservation of chromosomal stability

Barboza

Li²,

Zhang³

et al. 2006

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

100

156

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The p53 protein suppresses tumorigenesis by initiating cellular functions such as cell cycle arrest and apoptosis in response to DNA damage. A p53 mutant, p53R172P, which is deficient for apoptosis but retains a partial cell cycle arrest function, delays tumor onset in mice. Remarkably, lymphomas arising in Trp53 515C/515C mice (encoding p53R172P) retain stable genomes. Given the dominant role of p21 in p53 cell cycle control, we crossed Trp53 515C/515C mice onto a p21-null background to determine whether p21 was required for maintaining chromosomal stability and delaying tumor onset. Loss of p21 completely abolished the cell cycle arrest function of p53R172P and accelerated tumor onset in Trp53 515C/515C mice. Cytogenetic examination of Trp53 515C/515C p21 ؊/؊ sarcomas and lymphomas revealed aneuploidy and chromosomal aberrations that were absent in Trp53 515C/515C malignancies. Thus, p21 coupled p53-dependent checkpoint control and preservation of chromosomal stability, and cooperated with apoptosis in suppressing tumor onset in mice.apoptosis ͉ chromosomal instability ͉ p53 ͉ tumorigenesis ͉ mouse model T he role of p53 in tumor suppression is well established.

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“…6C). Activation of Ak1 and Wig1 by p53 can inhibit cellular proliferation (29,32,33). Our data suggest that these factors may also play important roles in p53 tumor suppression.…”

Section: Resultsmentioning

confidence: 75%

p21 delays tumor onset by preservation of chromosomal stability

Barboza

Li²,

Zhang³

et al. 2006

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

100

156

View full text Add to dashboard Cite

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“…In particular, ErbB-2 overexpression in human breast carcinomas has been correlated with up-regulation of p21 WAF1/CIP1 and poor response to chemotherapy (16). wig-1 encodes a putative RNA-binding zinc finger protein activated by p53 that induces growth arrest in colony formation assays (38,39). Other proteins up-regulated by the ATF included the tumor suppressors p14 ARF and hDMP1a, a transcription factor that directly activates p14 ARF transcription (41,42).…”

Section: Discussionmentioning

confidence: 99%

Modulation of drug resistance by artificial transcription factors

Blancafort

Tschan

Bergquist

et al. 2008

Molecular Cancer Therapeutics

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The efficiency of chemotherapeutic treatments in cancer patients is often impaired by the acquisition of drug resistance. Cancer cells develop drug resistance through dysregulation of one or more genes or cellular pathways. To isolate efficient regulators of drug resistance in tumor cells, we have adopted a genome-wide scanning approach based on the screening of large libraries of artificial transcription factors (ATFs) made of three and six randomly assembled zinc finger domains. Zinc finger libraries were linked to a VP64 activation domain and delivered into a paclitaxelsensitive tumor cell line. Following drug treatment, several ATFs were isolated that promoted drug resistance. One of these ATFs, 3ZF-1-VP, promoted paclitaxel resistance in cell lines having mutated or inactivated p53, such as MDA-MB-435 and Kaposi's sarcoma cell lines. 3ZF-1-VP also induced strong resistance to etoposide, vincristine, and cisplatinum. Linkage of a repression domain to the selected ATF resulted in enhanced sensitivity to multiple drugs, particularly vincristine, cisplatinum, and 5-fluorouracil. Small interfering RNA -mediated inhibition of p53 revealed that 3ZF-1-VP activated both p53-dependent and p53-independent mechanisms to promote survival, whereas other ATF required intact p53. Real-time expression analysis and DNA microarrays showed that several ATFs up-regulated targets of p53, such as the cyclin-dependent kinase inhibitor p21 WAF1/CIP1 , and genes participating in the p14 ARF

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“…6 We and others later cloned human Wig-1 and confirmed that it is a p53 target gene. 7,8 Human Wig-1 maps to chromosome 3q26.32. The Wig-1 protein exists in two isoforms differing by one amino acid only, and the Wig-1 open reading frame (ORF) translates into proteins of 288 or 289 amino acids.…”

Section: Structural and Functional Characteristics Of The Wig-1 Proteinmentioning

confidence: 99%

The p53 target Wig-1: a regulator of mRNA stability and stem cell fate?

et al. 2011

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Wig-1 is a transcriptional target of the tumor suppressor p53 and encodes an unusual zinc-finger protein involved in posttranscriptional gene regulation. Wig-1 is expressed in all cell types investigated so far, with the highest levels in the brain, and is enriched in stem cells as compared with more differentiated cells of the same lineage. Wig-1 binds to both long double-stranded (ds) RNA and short microRNA-like dsRNA. We have shown that Wig-1 acts in a positive feedback loop that stabilizes p53 mRNA through an AU-rich element (ARE) in the p53 3 0 untranslated region. Our preliminary data indicate a more general effect of Wig-1 on ARE-containing mRNA. Here we shall summarize current knowledge about Wig-1 and discuss possible implications on p53 function and other cellular processes.

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Human wig-1, a p53 target gene that encodes a growth inhibitory zinc finger protein

Cited by 58 publications

References 33 publications

p21 delays tumor onset by preservation of chromosomal stability

p21 delays tumor onset by preservation of chromosomal stability

Modulation of drug resistance by artificial transcription factors

The p53 target Wig-1: a regulator of mRNA stability and stem cell fate?

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