Official websites use. Share sensitive information only on official, secure websites. Correspondence: johannes. Although the complex network of S signalling is by far not fully deciphered, several S family members could be linked to a variety of diseases, such as inflammatory disorders, neurological diseases, and also cancer.
The research of the past decades revealed that S proteins play a crucial role in the development and progression of many cancer types, such as breast cancer, lung cancer, and melanoma. Hence, S family members have also been shown to be promising diagnostic markers and possible novel targets for therapy. However, the current knowledge of S proteins is limited and more attention to this unique group of proteins is needed. Therefore, this review article summarises S proteins and their relation in different cancer types, while also providing an overview of novel therapeutic strategies for targeting S proteins for cancer treatment.
In , Blake W. Moore isolated a protein from the bovine brain to identify specific proteins of the nervous system. Isobe et al. Further research from the past decades revealed that their expression was not limited to nervous tissue but that S proteins are found in various tissues exclusively in vertebrates. Subsequently, many more Srelated proteins were discovered, and currently, 25 family members are known [ 4 ]. It has since been shown that these proteins are involved in a variety of different pathways, thereby playing a critical role in essential cellular processes, such as proliferation, apoptosis, differentiation, and inflammation [ 5 ].
S proteins are classified as EF-hand motif calcium-binding proteins and represent the largest subgroup within the EF-hand superfamily [ 6 ]. SG is an exception to the rule, as it only exists as a monomer [ 7 , 8 ]. Van der Waals interactions stabilise the dimers, and the formation of higher-order oligomers is also observed [ 6 , 8 ]. The two EF-hands are connected by a hinge region [ 9 ], and helix I and helix IV display the dimerisation interface [ 10 ].
When calcium binds to loop II of the C-terminal EF-hand, the orientation of helix III shifts and exposes a hydrophobic pocket, which is necessary for target binding [ 6 , 7 , 11 ]. An S homodimer is usually supplied with two symmetrical hydrophobic binding sites that recognise two identical target molecules [ 7 , 10 , 12 ]. In this context, Nakashige et al. However, so far, this finding is ambiguous in comparison with previous studies [ 16 , 17 ].
