Figure 5.

Isoforms of proteins involved in apoptosis and whose splicing is controlled by SPFB1: (A) MCL is spliced to give at least three different isoforms. The long isoform is anti-apoptotic and binds pro-apoptotic proteins such as BAk, BIM and BID, preventing them from dimerising and permeabilising the mitochondrial membrane. The shorter form lacks the sequence coding for the initial part of the BCL domain, preventing the formation of the BCL domain. This shorter protein cannot therefore, associate with these proteins. The same is true of (B) BCL-x. The shorter version lacks most of the sequence coding for the BCL domain. This prevents the proper formation of the BCL domain and the shorter protein can therefore not bind pro-apoptotic BH3 domain proteins such as (C) BID. BID is spliced to give at least three isoforms. Here the longer isoform is the pro-apoptotic isoform that has a BH3 domain coded for by exon 2. This domain allows the protein to oligomerise with other BH3 members leading to permeabilization of the mitochondrial membrane. This ability is lost in the shorter truncated form.