%0 Journal Article
%T The Role of FIP-2 (optineurin) in Regulation of the Chemokines and Kinases - The Role of FIP-2 (optineurin) in Regulation of the Chemokines and Kinases - Open Access Pub
%A Leonid Tarassishin
%A Marshall S. Horwitz
%J OAP | Home | Journal of Proteomics and Genomics Research | Open Access Pub
%D 2018
%X FIP-2 is a multifunctional protein which is involved in various cellular processes. Using different approaches we investigated its regulatory activity. The microarray analysis has shown that FIP-2 substantially altered the expression of 75 genes (35+/40-) from different functional groups with maximal presentation in ¡°Signal transduction¡± and ¡°Transcription regulation¡±. Real time RT-PCR indicated significant elevation in the transcription of chemokines, particularly IL-8 (CXCL8). Production of IL-8 in HEK293 cells dramatically increased with FIP-2 overexpression. We also demonstrated that FIP-2 induced activation of IL-8 promoter activity through NF-kB binding site. Additionally, we showed that FIP-2 could interact with PAK3 and increase its kinase activity. Overall, we demonstrated the role of FIP-2 in the regulation of chemokines (IL-8, MPIF-1, MCP-1) and kinases (PAK3, ALK). DOI10.14302/issn.2326-0793.jpgr-13-355 FIP-2 (Fourteen point seven (14.7K) Interaction Protein-2) was originally detected during a yeast two-hybrid screening using an adenovirus early E3-coded protein, 14.7K, as bait 1. A few years later another protein named NEMO-related protein (NRP) was identified as a protein with partial homology to the well-known component of IKK complex, NEMO/IKK-gamma/FIP-3 2. At that time the data about the transcription factor IIIA-interacting protein also appeared 3. Finally, a protein named optineurin (OPTN) was detected during genetic analysis of individuals with adult-onset primary open-angle glaucoma 4. All these proteins have similar sequences and contain 577 amino acids (about 66 kDa) with high levels of Glu (15.8%), Leu (11.8%), Lys (9.4%), and Ser (8.0%). FIP-2 has a few domains such as coiled-coil, leucine zipper, ubiquitin-binding, and zinc finger 1, 4. FIP-2 is thought to be a multifunctional protein that participates in the development of primary open-angle glaucoma, amyotrophic lateral sclerosis, and Paget¡¯s disease of bone 5, 6. It is still not clear how gain or loss of functions of this protein leads to these and probably other neurodegenerative pathologies. It has been shown that FIP-2 interacts with several proteins such as huntingtin, Rab 8, myosin VI, transferring receptor, TANK-binding kinase 1, serine/threonine kinase receptor-interacting protein 1, metabotropic glutamate receptors, and transcription factor IIIA. FIP-2 is involved in various cellular functions, including cellular morphogenesis, membrane and vesicular trafficking, transcription activation, maintenance of the Golgi apparatus, signaling, and exocytosis 6. Our current
%U https://www.openaccesspub.org/jpgr/article/73