Multiple molecular forms of adaptor protein Ruk/CIN85 specifically associate with different subcellular compartments in human breast adenocarcinoma MCF-7 cells

• Published in: Ukrainian biochemical journal Vol. 86; no. 5; pp. 102 - 110
• Main Authors: Vynnytska-Myronovska, B O, Bobak, Ya P, Pasichnyk, G V, Igumentseva, N I, Samoylenko, A A, Drobot, L B
• Format: Journal Article
• Language: English
• Published: Ukraine National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry 01.09.2014
• Subjects: adaptor proteins; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Antibiotics, Antineoplastic - pharmacology; apoptosis; Apoptosis - drug effects; Cell Compartmentation; Cell Fractionation; DNA Fragmentation; Doxorubicin - pharmacology; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; multiple molecular forms; Organelles - chemistry; Organelles - drug effects; Organelles - metabolism; Protein Interaction Domains and Motifs; Protein Isoforms - genetics; Protein Isoforms - metabolism; Protein Processing, Post-Translational; Ruk/CIN85; Signal Transduction; subcellular distribution
• ISSN: 2409-4943; 2413-5003
• DOI: 10.15407/ubj86.05.102

Ruk/CIN85 is a receptor-proximal 'signalling' adaptor that possesses three SH3 domains, Pro- and Ser-rich regions and C-terminal coiled-coil domain. It employs distinct domains and motifs to act as a transducer platform in intracellular signaling. Based on cDNA analysis, various isoforms of Ruk/CIN85 with different combination of protein-protein interaction domains as well as additional Ruk/CIN85 forms that are the products of post-translational modifications have been demonstrated. Nevertheless, there is no precise information regarding both the subcellular distribution and the role of Ruk/CIN85 multiple molecular forms in cellular responses. Using MCF-7 human breast adenocarcinoma cells and cell fractionation technique, specific association of Ruk/CIN85 molecular forms with different subcellular compartments was demonstrated. Induction of apoptosis of MCF-7 cells by doxorubicin treatment or by serum deprivation resulted in the system changes of Ruk/CIN85 molecular forms intracellular localization as well as their ratio. The data obtained provide a new insight into potential physiological significance of Ruk/CIN85 molecular forms in the regulation of various cellular functions.