Functional impact of cancer patient-associated Bcl-xL mutations Journal Article


Authors: Zhang, T.; Na, J. H.; Li, S.; Chen, Z.; Zhang, G.; Pang, S. R.; Daniyan, A. F.; Li, Y.; Shi, L.; Du, Y. C. N.
Article Title: Functional impact of cancer patient-associated Bcl-xL mutations
Abstract: Bcl-xL, an antiapoptotic protein, is frequently overexpressed in cancer to promote survival of tumor cells. However, we have previously shown that Bcl-xL promotes migration, invasion, and metastasis independent of its antiapoptotic function in mitochondria. The pro-metastatic function of Bcl-xL may require its translocation into the nucleus. Besides overexpression, patient-associated mutations of Bcl-xL have been identified in large-scale cancer genomics projects. Understanding the functions of these mutations will guide the development of precision medicine. Here, we selected four patient-associated Bcl-xL mutations, R132W, N136K, R165W, and A201T, to investigate their impacts on antiapoptosis, migration, and nuclear translocation. We found that all four mutation proteins could be detected in both the nucleus and cytosol. Although all four mutations disrupted the antiapoptosis function, one of these mutants, N136K, significantly improved the ability to promote cell migration. These data suggest the importance of developing novel Bcl-xL inhibitors to ablate both antiapoptotic and pro-metastatic functions of Bcl-xL in cancer.
Keywords: gene; protein; migration; mutations; cells; specificity; binding; residues; bcl-xl; fluorescent; nucleus; bcl-x(l); platform; antiapoptosis
Journal Title: MedComm
Volume: 1
Issue: 3
ISSN: 2688-2663
Publisher: John Wiley & Sons  
Date Published: 2020-12-01
Start Page: 328
End Page: 337
Language: English
ACCESSION: WOS:000716863700006
DOI: 10.1002/mco2.36
PROVIDER: wos
PMCID: PMC8302207
PUBMED: 34308416
Notes: Article -- Source: Wos
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  1. Anthony   Daniyan
    31 Daniyan