YB-1 Phosphorylation at Serine 209 Inhibits Its Nuclear Translocation

Sogorina, Ekaterina M.; Kim, Yekaterina; Sorokin, Alexey V.; Lyabin, Dmitry N.; Ovchinnikov, Lev P.; Mordovkina, Daria A.; Eliseeva, Irina A.

doi:10.3390/ijms23010428

Cited by 7 publications

(5 citation statements)

References 55 publications

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“…In human breast and ovarian cancer cells, it has been reported that the S102 of YB-1 is phosphorylated by PI3K/Akt pathway, and this phosphorylation in turn induces nuclear translocation of YB-1 [22, 54] as well as its dissociation from the capped mRNAs, therefore increasing their translation [30]. Interestingly, in contrast to S102, the phosphorylation at S209 also by Akt inhibits YB-1 nuclear translocation [55].…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of zebrafish folliculogenesis identifies YB-1 (Ybx1/ybx1) as a potential gatekeeping molecule controlling early ovarian folliculogenesis

Lau

Zhu

Sun

et al. 2023

Biology of Reproduction

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As in mammals, ovarian folliculogenesis in teleosts also consists of two phases: the primary growth (PG) and secondary growth (SG) phases, which are analogous to the preantral and antral phases respectively in mammals. In this study, we performed a proteomic analysis on zebrafish follicles undergoing the PG-SG transition aiming to identify factors involved in the event. Numerous proteins showed significant changes, and the most prominent one was Y-box binding protein 1 (YB-1; Ybx1/ybx1), a transcription factor and mRNA-binding protein. YB-1 belongs to the Y-box binding protein family, which also includes the gonad-specific YB-2. Interestingly, phylogenetic analysis showed no YB-2 homologue in zebrafish. Although ybx1 mRNA was expressed in various tissues, its protein Ybx1 was primarily produced in the gonads, similar to YB-2 in other species. In the ovary, Ybx1 protein started to appear in early follicles newly emerged from the germ cell cysts, reached the highest level in late PG oocytes, but decreased precipitously when the follicles entered the SG phase. In PG follicles, Ybx1 might function as a key component of the messenger ribonucleoprotein particles (mRNP) in association with other RNA-binding proteins. Similar to mammalian YB-1, zebrafish Ybx1 also contains functional signals that determine its intracellular localization. In conclusion, Ybx1 may play dual roles of YB-1 and YB-2 in zebrafish. In the ovary, Ybx1 binds mRNAs to stabilize them while preventing their translation. At PG-SG transition, Ybx1 is removed to release the masked mRNAs for translation into functional proteins, leading to follicle activation.

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Section: Discussionmentioning

confidence: 99%

Proteomic analysis of zebrafish folliculogenesis identifies YB-1 (Ybx1/ybx1) as a potential gatekeeping molecule controlling early ovarian folliculogenesis

Lau

Zhu

Sun

et al. 2023

Biology of Reproduction

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“…Phosphorylation at S102 in the CSD region is the most widely reported post-translational modification of YB-1 [ 104 ]. In addition, YB-1 phosphorylation sites contain S30/34 [ 154 ], S176 [ 155 , 156 ], S165 [ 157 ], Y162 [ 158 , 159 , 160 ], S209 [ 161 ], and Y188 [ 162 ]. First, AKT [ 161 ], ERK [ 163 ], and RSK1/2 [ 106 ] were identified as kinases that directly phosphorylate YB-1.…”

Section: Upstream Regulation Of Yb-1mentioning

confidence: 99%

“…In addition, YB-1 phosphorylation sites contain S30/34 [ 154 ], S176 [ 155 , 156 ], S165 [ 157 ], Y162 [ 158 , 159 , 160 ], S209 [ 161 ], and Y188 [ 162 ]. First, AKT [ 161 ], ERK [ 163 ], and RSK1/2 [ 106 ] were identified as kinases that directly phosphorylate YB-1. Similarly, a number of factors that indirectly promote YB-1 phosphorylation were identified.…”

Section: Upstream Regulation Of Yb-1mentioning

confidence: 99%

YB-1 as an Oncoprotein: Functions, Regulation, Post-Translational Modifications, and Targeted Therapy

Yin

Zheng

Luo

et al. 2022

Cells

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Y box binding protein 1 (YB-1) is a protein with a highly conserved cold shock domain (CSD) that also belongs to the family of DNA- and RNA-binding proteins. YB-1 is present in both the nucleus and cytoplasm and plays versatile roles in gene transcription, RNA splicing, DNA damage repair, cell cycle progression, and immunity. Cumulative evidence suggests that YB-1 promotes the progression of multiple tumor types and serves as a potential tumor biomarker and therapeutic target. This review comprehensively summarizes the emerging functions, mechanisms, and regulation of YB-1 in cancers, and further discusses targeted strategies.

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“…4 D, E ) 41 , 42 . It remains to be tested whether other phosphorylations of YBX1 such as phospho-S209 43 affect the YBX1 function in tumour growth and invasion 44 , and in PIK3CA mutant HNC as seen in JAK2 mutant hematopoietic cancers 45 . In the absence of PI3K signalling, YBX1 binds to mRNAs of p-EMT markers in the cytoplasm 20 .…”

Section: Discussionmentioning

confidence: 99%

YBX1 integration of oncogenic PI3K/mTOR signalling regulates the fitness of malignant epithelial cells

et al. 2023

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In heterogeneous head and neck cancer (HNC), subtype-specific treatment regimens are currently missing. An integrated analysis of patient HNC subtypes using single-cell sequencing and proteome profiles reveals an epithelial-mesenchymal transition (EMT) signature within the epithelial cancer-cell population. The EMT signature coincides with PI3K/mTOR inactivation in the mesenchymal subtype. Conversely, the signature is suppressed in epithelial cells of the basal subtype which exhibits hyperactive PI3K/mTOR signalling. We further identify YBX1 phosphorylation, downstream of the PI3K/mTOR pathway, restraining basal-like cancer cell proliferation. In contrast, YBX1 acts as a safeguard against the proliferation-to-invasion switch in mesenchymal-like epithelial cancer cells, and its loss accentuates partial-EMT and in vivo invasion. Interestingly, phospho-YBX1 that is mutually exclusive to partial-EMT, emerges as a prognostic marker for overall patient outcomes. These findings create a unique opportunity to sensitise mesenchymal cancer cells to PI3K/mTOR inhibitors by shifting them towards a basal-like subtype as a promising therapeutic approach against HNC.

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YB-1 Phosphorylation at Serine 209 Inhibits Its Nuclear Translocation

Cited by 7 publications

References 55 publications

Proteomic analysis of zebrafish folliculogenesis identifies YB-1 (Ybx1/ybx1) as a potential gatekeeping molecule controlling early ovarian folliculogenesis

Proteomic analysis of zebrafish folliculogenesis identifies YB-1 (Ybx1/ybx1) as a potential gatekeeping molecule controlling early ovarian folliculogenesis

YB-1 as an Oncoprotein: Functions, Regulation, Post-Translational Modifications, and Targeted Therapy

YBX1 integration of oncogenic PI3K/mTOR signalling regulates the fitness of malignant epithelial cells

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