Transportin-1-dependent YB-1 nuclear import

Mordovkina, Daria A.; Kim, Yekaterina; Buldakov, Ilya A.; Sorokin, Alexey V.; Eliseeva, Irina A.; Lyabin, Dmitry N.; Ovchinnikov, Lev P.

doi:10.1016/j.bbrc.2016.10.107

Cited by 22 publications

(20 citation statements)

References 32 publications

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“…We suggest that the loss of the C-terminal region may lead to a similar conformational change in YB-1 making the NLS more accessible. It is also in agreement with data demonstrating that nuclear translocation of YB-1 is dependent on an intact NLS [52].…”

Section: Discussionsupporting

confidence: 92%

Dephosphorylation of YB-1 is Required for Nuclear Localisation During G2 Phase of the Cell Cycle

Mehta

McKinney

Algie

et al. 2020

Cancers

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Elevated levels of nuclear Y-box binding protein 1 (YB-1) are linked to poor prognosis in cancer. It has been proposed that entry into the nucleus requires specific proteasomal cleavage. However, evidence for cleavage is contradictory and high YB-1 levels are prognostic regardless of cellular location. Here, using confocal microscopy and mass spectrometry, we find no evidence of specific proteolytic cleavage. Doxorubicin treatment, and the resultant G2 arrest, leads to a significant increase in the number of cells where YB-1 is not found in the cytoplasm, suggesting that its cellular localisation is variable during the cell cycle. Live cell imaging reveals that the location of YB-1 is linked to progression through the cell cycle. Primarily perinuclear during G1 and S phases, YB-1 enters the nucleus as cells transition through late G2/M and exits at the completion of mitosis. Atomistic modelling and molecular dynamics simulations show that dephosphorylation of YB-1 at serine residues 102, 165 and 176 increases the accessibility of the nuclear localisation signal (NLS). We propose that this conformational change facilitates nuclear entry during late G2/M. Thus, the phosphorylation status of YB-1 determines its cellular location.

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Section: Discussionsupporting

confidence: 92%

Dephosphorylation of YB-1 is Required for Nuclear Localisation During G2 Phase of the Cell Cycle

Mehta

McKinney

Algie

et al. 2020

Cancers

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“…Indeed, we observed high basal expression of YB-1 in the nuclear fractions of lung, breast, and head and neck cancer cell lines, which is in line with the data published by Basaki et al in ovarian cancer cell lines [29]. Nuclear expression of YB-1 under non-stimulated conditions in the present study and the data reported by Basaki in ovarian cancer cells indicate that nuclear accumulation of YB-1 is a phenomenon that occurs gradually under basal stimulated conditions and, as reported, is regulated by Akt [28,29] and transportin-1 [30,31]. In the study by Basaki et al [29], the authors tested whether stress-inducing exogenous addition of serum could stimulate nuclear translocation of YB-1 in seven serum-deprived human ovarian cancer cell lines.…”

Section: Discussionsupporting

confidence: 93%

Stress-Induced Phosphorylation of Nuclear YB-1 Depends on Nuclear Trafficking of p90 Ribosomal S6 Kinase

Tiwari

Rebholz

Maier

et al. 2018

IJMS

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Ionizing radiation (IR) and epidermal growth factor (EGF) stimulate Y-box binding protein-1 (YB-1) phosphorylation at Ser-102 in KRAS wild-type (KRASwt) cells, whereas in KRAS mutated (KRASmut) cells, YB-1 is constitutively phosphorylated, independent of IR or EGF. YB-1 activity stimulates the repair of IR-induced DNA double-strand breaks (DSBs) in the nucleus. Thus far, the YB-1 nuclear translocation pattern after cell exposure to various cellular stressors is not clear. In the present study, we investigated the pattern of YB-1 phosphorylation and its possible translocation to the nucleus in KRASwt cells after exposure to IR, EGF treatment, and conditional expression of mutated KRAS(G12V). IR, EGF, and conditional KRAS(G12V) expression induced YB-1 phosphorylation in both the cytoplasmic and nuclear fractions of KRASwt cells. None of the stimuli induced YB-1 nuclear translocation, while p90 ribosomal s6 kinase (RSK) translocation was enhanced in KRASwt cells after any of the stimuli. EGF-induced RSK translocation to the nucleus and nuclear YB-1 phosphorylation were completely blocked by the EGF receptor kinase inhibitor erlotinib. Likewise, RSK inhibition blocked RSK nuclear translocation and nuclear YB-1 phosphorylation after irradiation and KRAS(G12V) overexpression. In summary, acute stimulation of YB-1 phosphorylation does not lead to YB-1 translocation from the cytoplasm to the nucleus. Rather, irradiation, EGF treatment, or KRAS(G12V) overexpression induces RSK activation, leading to its translocation to the nucleus, where it activates already-existing nuclear YB-1. Our novel finding illuminates the signaling pathways involved in nuclear YB-1 phosphorylation and provides a rationale for designing appropriate targeting strategies to block YB-1 in oncology as well as in radiation oncology.

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“…YB-1 is a nuclear-cytoplasmic shuttling protein whose subcellular localization is dictated by the nuclear localization signal (NLS, 186-205 a.a.) and the cytoplasmic retention signal (CRS, 267-293 a.a.) [56,207]. The YB-1 nuclear localization signal is considered as a PY-NLS recognized by transportin 1 [208,209]. Some other motifs, such as NLS-1 (149-156 a.a.), NLS-2 (185-194 a.a.), and NLS-3 (276-292 a.a.), can also influence YB-1 localization [168].…”

Section: Nuclear-cytoplasmic Transport Of Yb-1mentioning

confidence: 99%

Y-Box Binding Proteins in mRNP Assembly, Translation, and Stability Control

et al. 2020

Self Cite

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Y-box binding proteins (YB proteins) are DNA/RNA-binding proteins belonging to a large family of proteins with the cold shock domain. Functionally, these proteins are known to be the most diverse, although the literature hardly offers any molecular mechanisms governing their activities in the cell, tissue, or the whole organism. This review describes the involvement of YB proteins in RNA-dependent processes, such as mRNA packaging into mRNPs, mRNA translation, and mRNA stabilization. In addition, recent data on the structural peculiarities of YB proteins underlying their interactions with nucleic acids are discussed.

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Transportin-1-dependent YB-1 nuclear import

Cited by 22 publications

References 32 publications

Dephosphorylation of YB-1 is Required for Nuclear Localisation During G2 Phase of the Cell Cycle

Dephosphorylation of YB-1 is Required for Nuclear Localisation During G2 Phase of the Cell Cycle

Stress-Induced Phosphorylation of Nuclear YB-1 Depends on Nuclear Trafficking of p90 Ribosomal S6 Kinase

Y-Box Binding Proteins in mRNP Assembly, Translation, and Stability Control

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