AI Article Synopsis
- Protein ubiquitination is crucial for regulating processes like protein degradation and cellular signaling, with E3 ligases playing a key role in determining substrate specificity.
- A study analyzed 82 ubiquitin ligases across nine cancer types and found that 27 ligases were misregulated, with most showing overexpression.
- Further analysis in breast and lung cancers revealed significant correlations between certain ligase levels and important prognostic indicators, highlighting these ligases as potential targets for cancer therapies.
Article Abstract
Protein ubiquitination is critical for many cellular processes, through its ability to regulate protein degradation and various signaling mechanisms. In the ubiquitin (Ub) system, substrate specificity is achieved through the E3 family of Ub ligases. Because alterations of the ubiquitination machinery have been reported in human cancers, the selective interference with Ub ligases might represent a powerful therapeutic tool. Here, we report the first wide survey of misregulation of Ub ligases in cancer. We analysed 82 Ub ligases in nine types of cancer by in situ hybridization on tissue microarrays. We found 27 instances in which an Ub ligase was altered in a given type of tumor, when compared with normal tissues: 21 cases of overexpression and 6 cases of underexpression. We further analysed selected Ub ligases in large cohorts of breast and non-small-cell lung carcinomas. In five, of six, of these extended analyses (HUWE1, CCNB1IP1, SIAH1 and SIAH2 in breast cancer and CCNB1IP1 in lung cancer), we found that the levels of Ub ligases correlated significantly with relevant prognostic factors, and with clinical outcome. Our findings show that the alteration of Ub ligases is a frequent event in cancer and identify candidate targets for molecular therapies.
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| http://dx.doi.org/10.1038/onc.2009.156 | DOI Listing |
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