studies have been preformed with Bim as this BH3 only protein can complex with Bcl 2 and Bcl xL to the endogenous level. Recent studies suggested that Hrk DP5 is transcriptionally activated via the JNK pathway. Nevertheless, many interaction studies have been performed with overexpressed proteins, and the binding affinities between a Bcl 2 and a particular BH3 protein or Bax like issue have not yet been determined. We therefore do not yet know which of the possible relationships are physiologically relevant. More over, Bim knock-out mice exert a similar phenotype Tipifarnib R115777 as mice that carry a Bcl 2 transgene. They create lymphoproliferative conditions including leukemias and are resistant to apoptosis induced by cytokine and growth factor deprivation. Most significantly, erasure of Bcl 2 can rescue the Bim knock out phenotype indicating that Bim somehow must act via Bcl 2 and does not moreover need Bax or Bak for the professional apoptotic activity. It does not explain various new findings, although this model is compelling. Firstly, while bad choice of thymocytes is only Immune system slightly impacted in Bcl 2 and Bcl xL transgenic mice, it is really ablated in Bim knock out animals. This indicates that Bim elicits a pro apoptotic activity in addition to its binding to Bcl 2 and Bcl xL. Secondly, only a few molecules of Bim may induce apoptosis even in the presence of large levels of Bcl 2 and Bcl xL. Strasser et al. explained this phenomenon by way of a prion like design, in a way that a small quantity of Bim may nucleate the polymerization and inactivation of many Bcl 2 and Bcl xL molecules. Nevertheless, there is currently no evidence for this kind of model once we have recently demonstrated that Bcl 2 or Bcl xL don’t di or oligomerize in a reaction to apoptotic stimuli. Instead, the affinity of Bim for Bcl 2 like success factors could be stronger than that of Bax and CED 4 like factors. In this instance, even small amounts of Bim would suffice release a these pro apoptotic factors k63 ubiquitin in the face of Bcl 2 like survival factors. Recent studies on Bax / /Bak double knock-out mice recommended that BH3 only proteins may also directly interact with Bax like facets to help their translocation, conformational change, oligomerization and mitochondrial membrane insertion. While individual knock outs do not present significant problems, the double knock out dies in utero with gross finds in brain development. Moreover, cells isolated from these animals are resistant to various apoptotic stimuli indicating that either Bax or Bak are important for apoptosis under numerous situations. Most of all, a variety of BH3 only proteins such as Bad, Bim and Bid were unable to induce apoptosis when expressed in Bax/Bak double deficient cells.