English

Abstract

Introduction The BH3-only family members BID is a pro-apoptotic protein of the Bcl-2 family that is crucial for mitochondria-mediated apoptosis in many cell systems. However, some recent studies have found that BID may also play a pro-survival role. It can be the intermediate substance of deoxyribonucleic acid damage response, which is connected with the phosphorylation of BID. Likewise, BID−/− cells in mice decrease the release of inflammatory factors. BID is also a mediator of inflammation. Hypothesis Based on the above point of view, we hypothesize that BID, a novel convergent molecular, is a potential link between the inflammation and the irrepairable deoxyribonucleic acid damage responses in tumourigenesis. Evaluation of hypothesis There is clear evidence that inflammation plays a critical role in tumourigenesis, and some of the molecular mechanisms have been elucidated, which show that the inflammation in tumourigenesis is related to the deoxyribonucleic acid damage. Inflammatory cells turn into cancer cells when their deoxyribonucleic acid is destroyed. Most of the times, damaged deoxyribonucleic acid is repaired by BID phosphorylation by the kinase ataxia-telangiectasia mutated involved in the deoxyribonucleic acid repair response. But if it is not repaired, the damaged deoxyribonucleic acid initiates the apoptosis of cells or the organs or tumourigenesis. Moreover, BID drives the production of pro-inflammation cytokine and chemokines resulting in either increasing of stressed cells or a local inflammatory response. So, we consider that inflammation depends on BID to link Deoxyribonucleic acid damage response. Conclusion BID plays a key regulatory role in both the inflammation and deoxyribonucleic aciddamage responses. However, such as tBID, p-BID acts as its work forms may be activated in different, time. In brief, BID, a novel convergent molecular, is a potential link between the inflammation and the irrepairable deoxyribonucleic acid damage responses in tumourigenesis. However, much more work needs to be done to demonstrate the hypothesis. Introduction BID was originally discovered as a binding partner of both Bcl-2 and Bax, and later identified as a substrate of apical caspase-8 in the apoptotic pathways1. The cleaved BID (tBID) by the caspase-8 is an active form, which is modified by myristoylation and translocates into mitochondria, where it activates oligomerisation of Bak or Bax and promotes the release of cytochrome c. Cytochrome c in turn activates the apoptotic cascade of caspases-9 and -3, leading to cell death2–6. BID proapoptotic function has been identified and acknowledged7,8. However, according to BID structure, we believe that the function of BID has not been conclusively demonstrated, as for several other aspects of BID activation and function that have been outlined here8,9. The network of BID in the inflammatory response has been internality elucidated by Saleh Yeretssian et al.10. Conjunction with other studies indicates that the function of BID in inflammation and immunity is independent of its apoptotic function11–14, and BID is at the centre of the cellular decision to induce innate immune responses or commit suicide by apoptosis2–7,10. Depletion of BID leads to a marked reduction in interleukin (IL)8 production. Meanwhile, IL-6 production was significantly blunted in BID-deficient macrophages. Both of them inhibit activation of NF-κB and MAPKs (ERK1/2, p38 and JNK) pathways10. Interestingly, this paper has observed that BID phosphorylation by casein kinases I and II on serine residues proximal to the cleavage site hampers its processing and promotes cell survival. When HT-29 cells are treated by the NOD1 activator γ Tri-DAP, BID is not cleaved but phosphorylated. Mutation of phosphorylation sites in BID (BIDS64A, BIDS65A and BIDS78A) significantly blunted MDPinduced IL-6 production. Contemporarily, compared BID−/− mice with WT mice, the pronounced peritonitis was marked by infiltration of Gr11+ neutrophils when treated with γTriDAP10. Thus, BID phosphorylation is related to the inflammation, and at the same time it survives the cells. Simultaneously, BID is also involved in DNA damage response15–19.DNA damage leads to generation of DNA singleand double-strand breaks (DSBs). DSBs activate downstream DNA damage response pathways mediated by the phosphoinositide * Corresponding author Email: gangsongsd@xmu.edu.cn Cancer Research Center, Medical College of Xiamen University, Xiamen 361102, China