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Siva-1 emerges as a tissue-specific oncogene beyond its classic role of a proapoptotic gene

Authors Vachtenheim J Jr, Lischke R, Vachtenheim J

Received 4 May 2018

Accepted for publication 25 July 2018

Published 1 October 2018 Volume 2018:11 Pages 6361—6367

DOI https://doi.org/10.2147/OTT.S173001

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Takuya Aoki


Jiri Vachtenheim, Jr,1 Robert Lischke,1 Jiri Vachtenheim2

1Third Department of Surgery, First Faculty of Medicine, Charles University Prague and University Hospital Motol, Prague, Czech Republic; 2Department of Transcription and Cell Signaling, Institute of Medical Biochemistry and Laboratory Diagnostics, Charles University Prague, Czech Republic

Abstract: Siva-1 is a typical apoptotic protein commonly activated by the p53 tumor suppressor protein and should therefore participate in a barrier against the development of cancer. It has proapoptotic activities in various cell systems. Recent findings suggest that Siva-1 possesses several other apoptosis-independent functions and interacts with many other proteins not directly involved in apoptosis. It harbors the ARF E3 ubiquitin protein ligase activity, a property that is clearly prooncogenic and leads to p53 degradation through the upregulation of the Hdm2 protein level. Surprisingly, recent evidence shows that Siva-1 absence prevents the development of non-small cell lung carcinomas in a mouse model and reveals the oncogenic roles in the same types of human cells, indicating its unique function as an oncogene in the cell context-dependent manner. Herein, we review reported activities of Siva-1 in various experimental settings and comment on its ambiguous function in tumor biology.

Keywords: Siva-1, apoptosis, CD27, p53, NSCLC

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