Inhibition of Transcription Induces Phosphorylation of YB-1 at Ser102 and Its Accumulation in the Nucleus

转录抑制诱导YB-1 Ser102位点磷酸化及其在细胞核内的积累

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作者:Dmitry A Kretov, Daria A Mordovkina, Irina A Eliseeva, Dmitry N Lyabin, Dmitry N Polyakov, Vandana Joshi, Bénédicte Desforges, Loic Hamon, Olga I Lavrik, David Pastré, Patrick A Curmi, Lev P Ovchinnikov

Abstract

The Y-box binding protein 1 (YB-1) is an RNA/DNA-binding protein regulating gene expression in the cytoplasm and the nucleus. Although mostly cytoplasmic, YB-1 accumulates in the nucleus under stress conditions. Its nuclear localization is associated with aggressiveness and multidrug resistance of cancer cells, which makes the understanding of the regulatory mechanisms of YB-1 subcellular distribution essential. Here, we report that inhibition of RNA polymerase II (RNAPII) activity results in the nuclear accumulation of YB-1 accompanied by its phosphorylation at Ser102. The inhibition of kinase activity reduces YB-1 phosphorylation and its accumulation in the nucleus. The presence of RNA in the nucleus is shown to be required for the nuclear retention of YB-1. Thus, the subcellular localization of YB-1 depends on its post-translational modifications (PTMs) and intracellular RNA distribution.

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