CacyBP/SIP - Structure and variety of functions

Background: CacyBP/SIP (Calcyclin-Binding Protein and Siah-1 Interacting Protein) is a small modular protein implicated in a wide range of cellular processes. It is expressed in different tissues of mammals but homologs are also found in some lower organisms. In mammals, a high level of CacyBP/SIP is present in tumor cells and in neurons. CacyBP/SIP binds several target proteins such as members of the S100 family, components of a ubiquitin ligase complex, and cytoskeletal proteins. Scope of review: CacyBP/SIP has been shown to be involved in protein de-phosphorylation, ubiquitination, cytoskeletal dynamics, regulation of gene expression, cell proliferation, differentiation, and tumorigenesis. This review focuses on very recent reports on CacyBP/SIP structure and function in these important cellular processes. Major conclusions: CacyBP/SIP is a multi-domain and multi-functional protein. Altered levels of CacyBP/SIP in several cancers implicate its involvement in the maintenance of cell homeostasis. Changes in CacyBP/SIP subcellular localization in neurons of AD brains suggest that this protein is strongly linked to neurodegenerative diseases. Elucidation of CacyBP/SIP structure and cellular function is leading to greater understanding of its role in normal physiology and disease pathologies. General significance: The available results suggest that CacyBP/SIP is a key player in multiple biological processes. Detailed characterization of the physical, biochemical and biological properties of CacyBP/SIP will provide better insight into the regulation of its diverse functions in vivo, and given the association with specific diseases, will help clarify the potential of therapeutic targeting of this protein. (C) 2015 Elsevier B.V. All rights reserved.