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Review
. 2018 Oct 1:11:6361-6367.
doi: 10.2147/OTT.S173001. eCollection 2018.

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

Jiri Vachtenheim Jr  1 , Robert Lischke  1 , Jiri Vachtenheim  2
Affiliations
Review

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

Jiri Vachtenheim Jr et al. Onco Targets Ther. .

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: CD27; NSCLC; Siva-1; apoptosis; p53.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Siva-1-interacting proteins. Note: Arrows show the Siva-1-interacting proteins connected to apoptosis or carcinogenesis (the abbreviation of each protein and the description of molecular mechanisms is described in the text). Abbreviations: TNFR, tumor necrosis factor receptor; GITR, glucocorticoid-induced tumor necrosis factor receptor; mitoch., mitochondria.
See this image and copyright information in PMC

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