The WTX Tumor Suppressor Enhances p53 Acetylation by CBP/p300

Woo Jae Kim et al., Molecular Cell 45, 587–597( 2012)

Speaker: Zih-Cian Su(蘇資茜)                                            Time:10/24/2012, 2:00-3:00 PM

Commentator: Pai-Sheng Chen, Ph.D (陳百昇老師)       Location: Room 601

Abstract

In 1972, Knudson and Strong proposed that Wilms tumor, like retinoblastoma, may develop as a consequence of two independent rate-limiting genetic events, subsequently defined as biallelic inactivation of a tumor-suppressor gene, WT1. Although inactivation of WT1 affects only a small subset of cases, according to previous studies there was a deletion of chromosome locus Xq11 in some patients (up to 1/3 of sporadic Wilms tumor). This uncharacterized gene was named WTX. Several studies have reported distinct functions of WTX in different cellular compartments. In the cytoplasm, WTX downregulates the WNT signaling pathway by promoting ubiquitination and degradation of β-catenin. In the nucleus WTX modulates nuclear WT1 transcription activation .In this study, authors observed a strong correlation between WTX and p53 activation by microarray . The adenovirus protein E1B 55K is remarkable in that it suppresses p53-mediated transactivation. HEK293 cells tolerate high levels of endogenous p53 owing to inactivation by the adenoviral E1B 55K oncoprotein, in part through sequestration in the characteristic cytoplasmic E1B body. They found that WTX expression triggers disruption of the characteristic adenovirus E1B body in adenovirus-transformed HEK293 cells and release of p53 into the nucleus. In addition, WTX modulates p53 acetylation through its stabilization of acetyltransferase CBP/p300 , as well as its enhancement of the CBP/p300-p53 complex.. Thus, on one hand WTX negatively regulates the oncogenic WNT/β-catenin signaling pathway; on the other hand WTX positively regulates the classic p53 tumor suppressor pathway.

References

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