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Review
. 2014 Dec 23:9:44.
doi: 10.1186/1750-9378-9-44. eCollection 2014.

Disruption of Bcl-2 and Bcl-xL by viral proteins as a possible cause of cancer

Kenneth Alibek  1 , Stephanie Irving  2 , Zarina Sautbayeva  2 , Ainur Kakpenova  2 , Aliya Bekmurzayeva  2 , Yeldar Baiken  2 , Nurgul Imangali  3 , Madina Shaimerdenova  3 , Damel Mektepbayeva  2 , Arnat Balabiyev  2 , Aizada Chinybayeva  2
Affiliations
Review

Disruption of Bcl-2 and Bcl-xL by viral proteins as a possible cause of cancer

Kenneth Alibek et al. Infect Agent Cancer. .

Abstract

The Bcl proteins play a critical role in apoptosis, as mutations in family members interfere with normal programmed cell death. Such events can cause cell transformation, potentially leading to cancer. Recent discoveries indicate that some viral proteins interfere with Bcl proteins either directly or indirectly; however, these data have not been systematically described. Some viruses encode proteins that reprogramme host cellular signalling pathways controlling cell differentiation, proliferation, genomic integrity, cell death, and immune system recognition. This review analyses and summarises the existing data and discusses how viral proteins interfere with normal pro- and anti-apoptotic functions of Bcl-2 and Bcl-xL. Particularly, this article focuses on how viral proteins, such as Herpesviruses, HTLV-1, HPV and HCV, block apoptosis and how accumulation of such interference predisposes cancer development. Finally, we discuss possible ways to prevent and treat cancers using a combination of traditional therapies and antiviral preparations that are effective against these viruses.

Keywords: Apoptosis; Bcl-2; Bcl-xL; Cancer; Hepatitis C virus; Herpesviruses; Human T-lymphotropic virus 1; Human papillomavirus; Signaling pathways; Tumor suppressor genes.

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Figures

Figure 1
Figure 1
(a) Apoptotic cell death pathways and (b) inhibition of the apoptosis signalling pathway.
Figure 2
Figure 2
EBV interaction with the Bcl family. BHRF1 is the viral structural and functional homologue of the human proto-oncogene Bcl-2 and is able to blockcell death through repression of pro-apoptotic proteins BIM, PUMA, and BID and upregulation of Bcl-2 [15, 21]. Activated BARF1 upregulates Bcl-2 protein levels [15]. LMP-1 upregulates Bcl-2 expression through the NF-κB/c-JNK/AP-1 pathway, while LMP2A increases expression of Bcl-xL and Bcl-2 through the Ha-Ras, PI3K/Akt, NF-κB and Raf/MEK/ERK pathways, respectively [15]. BZLF1 represses CD74 and p65 resulting in downregulation of Bcl-2 and Bcl-xL expression [15]. EBER1 and EBER2 allow c-MYC to stimulate oncogenesis and inhibit apoptosis [15].
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