Nuclear shuttling of Y Box binding protein-1, its clinical relevance in cancer and as a therapeutic target

Abstract

Y-box binding protein 1 (YB-1) is an imperative biomarker for the clinical outcome of cancer patients. An overexpression of YB-1 in cancerous and adjoining tissues is an indication of aggressiveness and advanced stages. In normal resting cells, YB-1 is localized in cytoplasm while in stress conditions like cancer, nuclear shuttling of YB-1 takes place. In this review, the clinical importance of YB-1 in different cancers and the mechanism behind YB-1 nuclear shuttling have been discussed in detail. Targeted chemotherapies or molecularly targeted drugs of great importance can target and block specific molecules implicated in tumor growth and progression. YB-1 has been considered as a bonafide oncogene and accumulating evidences show the therapeutic importance of YB-1. Therapeutic strategies targeting YB-1 may improve the survival rate in cancer patients. This review extensively discusses the therapeutic importance of YB-1. Article InfoReceived:16 Mini-reviewThis article was downloaded by you on: Apr 30, 2016 In normal resting cells, full length YB-1 is mainly present in the cytoplasm of cells under stress during pathological conditions including inflammation, oxidative stress and cancer conditions. Particular segment of the YB-1 flips to the nucleus (Koike et al., 1997;Higashi et al., 2011).In this review, with the nuclear shuttling, clinical significance of YB-1 in cancer and as a therapeutic target have been evaluated from the existing literature. The present literature analysis shows the prospective role of YB-1 in cancer progression and drug resistance which could be harnessed to make it a promising therapeutic target. Nuclear shuttling of YB-1Since a number of functions have been assigned to YB-1, therefore, the sub-cellular protein shuttling needs to be highly stringent. In general, specific nuclear export signals and nuclear localization signals (NLS) contribute and direct the multifunctional shuttling and tasking (Bader and Vogt, 2005). Literature suggests three nuclear localization signals in YB-1 i.e. NLS1 (aa149-55), NLS2 (aa185-94) and NLS3 (276-92) (van Roeyen et al., 2013). The NLS3 is bipartite in composition and both the parts are essential for functionality. Irrespective of this, the changes of the spatial organization of 2 parts doesn't affect nuclear shuttling. Both NLS2 and NLS3 are essential for functionality and contain tyrosine residues which are required for phosphorylation. The full length YB-1 phosphorylated at tyrosine 281 in NLS3 has been found to be localized in the nucleus while the unphosphorylated YB-1 localized in the cytoplasm. This indicates that the phosphorylation at T-281 renders complete YB-1 to be localized in nucleus under normal conditions (van Roeyen et al., 2013). At the time of stress or cell stimulation, nuclear flipping of shortened YB-1 having N-terminal portion of the proteins takes place through a highly regulated process (Bader and Vogt, 2005;van Roeyen et al., 2013). Jürchott et al. (2003) suggested that the both C-terminal and cold shock domain of YB...

Long noncoding RNA HOTAIR interacts with Y-Box Protein-1 (YBX1) to regulate cell proliferation

“…YBX1 is a 36 kD protein composed of an N-terminal alanine/proline-rich domain (A/PD), a C-terminal domain (CTD), as well as a CSD (Fig 3A) (Lyabin et al, 2014). The CSD region is similar to cold shock proteins found in bacteria with respect to its tertiary structure (Kloks et al, 2002), whereas the A/PD and CTD regions are thought to lack any intrinsic structure (Kloks et al, 2002;Gunasekaran et al, 2016). The TriFC results showed that all three YBX1 domains could interact with HOTAIR (Fig 3B).…”