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HtrA1 sensitizes ovarian cancer cells to cisplatin-induced cytotoxicity by targeting XIAP for degradation by Xiaoping He; Ashwani Khurana; Jacie L Maguire; Jeremy Chien; Viji Shridhar is a Medicine article available to read on EtoBox.

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## Abstract HtrA1, a member of serine protease family, has been previously found to be involved in resistance to chemotherapy in ovarian cancer although the underlying mechanism is not clear. Using mixture‐based oriented peptide library approach, previously we identified X‐linked inhibitor of apoptosis protein (XIAP), a member of the inhibitor of apoptosis proteins family, as a potential substrate of HtrA1. The aim of our work is to investigate the link between HtrA1 and XIAP proteins and their relationships with chemoresistance in ovarian cancer. Our results showed that recombinant XIAP was degraded by purified wild‐type HtrA1 but not mutant HtrA1 __in vitro__. Consistent with the __in vitro__ data, coimmunoprecipitation assays showed that HtrA1 and XIAP formed a protein complex __in vivo__. Ectopic expression of HtrA1 led to decreased level of XIAP in OV167 and OV202 ovarian cancer cells, while knockdown of HtrA1 resulted in increased level of XIAP in SKOV3 ovarian cancer cells. Furthermore, overexpression of HtrA1 in OV202 cells promoted cell sensitivity to cisplatin‐induced apoptosis that could be reversed by increased expression of XIAP. The cleavage of XIAP induced by HtrA1 w

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Author

Xiaoping He; Ashwani Khurana; Jacie L Maguire; Jeremy Chien; Viji Shridhar

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley; Research Square; Test accounts (ISSN 0020-7136)

Published

2011

Language

EN

Field

Medicine (Health Sciences)