Abstract
YB-1 is a multifunctional DNA- and RNA-binding protein involved in cell proliferation, differentiation, and migration. YB-1 is a predominantly cytoplasmic protein that is transported to the nucleus in certain conditions, including DNA-damaging stress, transcription inhibition, and viral infection. In tumors, YB-1 nuclear localization correlates with high aggressiveness, multidrug resistance, and a poor prognosis. It is known that posttranslational modifications can regulate the nuclear translocation of YB-1. In particular, well-studied phosphorylation at serine 102 (S102) activates YB-1 nuclear import. Here, we report that Akt kinase phosphorylates YB-1 in vitro at serine 209 (S209), which is located in the vicinity of the YB-1 nuclear localization signal. Using phosphomimetic substitutions, we showed that S209 phosphorylation inhibits YB-1 nuclear translocation and prevents p-S102-mediated YB-1 nuclear import.
Highlights
YB-1 is a multifunctional protein involved in numerous cellular processes, including cell proliferation, differentiation, and migration
Our observations are in agreement with high-throughput data for mouse adipocytes [29], where the levels of p-serine 102 (S102) (S100 in mice) and p-serine 209 (S209) (S207 in mice)-containing peptides of YB-1 increased six-fold and four-fold, respectively, upon insulin stimulation. This suggests that both S102 and S209 can be phosphorylated in vivo by insulin-activated kinases, including but not limited to Akt
We have found that S209 phosphorylation prevents YB-1 nuclear translocation in vitro
Summary
YB-1 is a multifunctional protein involved in numerous cellular processes, including cell proliferation, differentiation, and migration (reviewed in [1,2]). The most studied posttranslational modifications are the S102, S165, and S176 residues phosphorylated by Akt/RSK, casein kinase. II, and casein kinase I, respectively [8–10,22–25] The phosphorylation at these residues promotes YB-1 nuclear translocation [8–10,23,26]. Sci. 2022, 23, 428 and casein kinase I, respectively [8–10,22–25] In some cell lines, phosphorylated YB-1 YB-1 does not translocate to the nucleus. Could pohttps://www.phosphosite.org [27], v6.6.0.2, accessed on 30 December 2021) and could tentially affect This residue is located in translocation is negatively regulated by S209 phosphorylation. In close vicinity downstream of YB-1 NLS and is phosphorylated by Akt kinase in vitro. Prevents YB-1 nuclear translocation even in the presence of phosphorylated S102
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
