BID

Case Study 1: Jordi Bertran-Alamillo, 2023

Drugs targeting the spindle assembly checkpoint (SAC), such as inhibitors of Aurora kinase B (AURKB) and dual specific protein kinase TTK, are in different stages of clinical development. However, cell response to SAC abrogation is poorly understood and there are no markers for patient selection.

The effects of drugs were analyzed by MTT and flow cytometry. Copy number status was determined by FISH and Q-PCR; mRNA expression by nCounter and RT-Q-PCR and protein expression by Western blotting. CRISPR-Cas9 technology was used for gene knock-out (KO) and a doxycycline-inducible pTRIPZ vector for ectopic expression. Tumor cells and patient-derived xenografts (PDXs) sensitive to AURKB and TTK inhibitors consistently showed high expression levels of BH3-interacting domain death agonist (BID), while cell lines and PDXs with low BID were uniformly resistant. Gene silencing rendered BID-overexpressing cells insensitive to SAC abrogation while ectopic BID expression in BID-low cells significantly increased sensitivity. A prevalence study revealed high BID mRNA in 6% of human solid tumors.

Fig1. Levels of four Chr22q11-codified proteins (B2L13, BID, CRKL and Erk1) in PC9 and 11-18 derived clones.

Fig2. Correlation between the levels of BID protein and BID mRNA ectopic expression in PC9-SE1 and SE2 colonies.

Case Study 2: Luciana R Muniz-Bongers, 2021

During apoptosis, the BCL-2-family protein tBID promotes mitochondrial permeabilization by activating BAX and BAK and by blocking anti-apoptotic BCL-2 members. Here, the researchers report that tBID can also mediate mitochondrial permeabilization by itself, resulting in release of cytochrome c and mitochondrial DNA, caspase activation and apoptosis even in absence of BAX and BAK. This previously unrecognized activity of tBID depends on helix 6, homologous to the pore-forming regions of BAX and BAK, and can be blocked by pro-survival BCL-2 proteins. Importantly, tBID-mediated mitochondrial permeabilization independent of BAX and BAK is physiologically relevant for SMAC release in the immune response against Shigella infection. Furthermore, it can be exploited to kill leukaemia cells with acquired venetoclax resistance due to lack of active BAX and BAK. These findings define tBID as an effector of mitochondrial permeabilization in apoptosis and provide a new paradigm for BCL-2 proteins, with implications for anti-bacterial immunity and cancer therapy.

Fig3. Kinetics of the expression of tBID-GFP (blue) and PI intake upon tBID expression (purple) and untransfected HCT116 AKO cells (in grey).

Fig4. Representative western blot analysis of BID, BAX and BAK expression levels in Nalm6, Nalm6 199R, Nalm6 199R BID KO #clone1 and Nalm6 199R BID KO #clone5.

Fig1. Schematic depicting the hypothetical transduction pathways triggered by TTK and AURKB inhibitors in cancer cells. (Jordi Bertran-Alamillo, 2023)

Fig2. Mitochondria metabolism regulates the fate of haematopoietic stem cells. (Atan Gross, 2016)

BID involved in several pathways and played different roles in them. We selected most pathways BID participated on our site, such as Sphingolipid signaling pathway, p signaling pathway, Apoptosis, which may be useful for your reference. Also, other proteins which involved in the same pathway with BID were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

BID has several biochemical functions, for example, death receptor binding, protein binding, ubiquitin protein ligase binding. Some of the functions are cooperated with other proteins, some of the functions could acted by BID itself. We selected most functions BID had, and list some proteins which have the same functions with BID. You can find most of the proteins on our site.

BID has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with BID here. Most of them are supplied by our site. Hope this information will be useful for your research of BID.

BCL2; BCL2L1; BAX