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Companion Diagnostics for Oncogenic Fusion Proteins
Published in Il-Jin Kim, Companion Diagnostics (CDx) in Precision Medicine, 2019
Roman Groisberg, Vivek Subbiah
A common oncogenic fusion involves the amalgamation of a kinase with another gene resulting in constitutive activation of the kinase. For example, the FGFR3–BAIAP2L1 fusion in bladder cancer causes constitutive Bin–Amphiphysin–Rvs (BAR) domain dimerization and resultant kinase activation independent of a binding ligand.4 Other oncogenic fusions result in over-expression of a kinase such as PDGFR by an overactive regulatory element. Such fusions are common in hematologic malignancies.5 Most of these kinase fusions will lead to downstream activation of cell proliferation and survival pathways such as MAPK and PI3K. These types of oncogenic fusions are typically the most clinically targetable by drugs.
Golgi apparatus regulation of differentiation
Published in C. Yan Cheng, Spermatogenesis, 2018
Louis Hermo, Regiana L. Oliveira, Charles E. Smith, Catherine E. Au, John J. M. Bergeron
Islet cell auto antigen 1-like protein (ICA1L), which has sequence similarities to ICA69 (also known as ICA1), has been identified as a BAR-domain binding partner (Bin, amphiphysin, Rvs) of PICK1 that is crucial for acrosome formation. ICA1L and PICK1 are highly expressed in spermatids and traffic together at different steps of spermiogenesis. ICA1L-knockout mice reveal that PICK1 expression is reduced by 80% in the testes of these mice. Sperm from ICA1L-knockout mice have abnormalities in the acrosome, nucleus, and flagellar mitochondrial sheath formation. Both total and motile sperm numbers are reduced and about half of the remaining sperm have the characteristics of globozoospermia. These defects ultimately result in reduced fertility of male ICA1L-knockout mice. ICA69/ICA1L-double knockout male mice are sterile.163
Dstac is required for normal circadian activity rhythms in Drosophila
Published in Chronobiology International, 2018
I-Uen Hsu, Jeremy W. Linsley, Jade E. Varineau, Orie T. Shafer, John Y. Kuwada
The Stac proteins are defined by the unique combination of a SH3 and CRD (Suzuki et al. 1996). The stac genes are found widely both in vertebrate and invertebrate lineages. In most vertebrate genomes there is a small family of stac genes with stac3 selectively expressed by skeletal muscles while the other stacs are expressed within the nervous system. In Drosophila, there appears to be a single stac gene. The conclusion that Dstac is a stac gene is based upon the presence of highly conserved SH3 and CRD of the predicted Dstac protein along with the expression of Dstac by both muscles and neurons. The latter is concordant with the expression of vertebrate stac3 by skeletal muscles and the other vertebrate stacs by neurons. One difference between invertebrate stac genes and vertebrate stac genes is the presence of a BAR domain. BAR domains are associated with membrane curvature (reviewed in Salzer et al. 2017) but the significance of the BAR domain in invertebrate stacs including Dstac is unknown. Interestingly, in vertebrates the Bin1 protein from which the BAR domain draws its name contains both BAR and a SH3 domain and like Stac3, associates with Cav1.1 in skeletal muscle where its BAR domain is associated with the formation of T-tubules in muscle (Lee et al. 2002). Mutations in the BAR domain of bin1 destabilize T-tubules and are associated with centronuclear myopathy in humans (Claeys et al. 2010). Thus the BAR domain may be critical to the function of Dstac in invertebrate muscle.