Y box binding protein 1 (YB-1) oncoprotein at the hub of DNA proliferation, damage and cancer progression

Sangermano, Felicia; Delicato, Antonella; Calabrò, Viola

doi:10.1016/j.biochi.2020.10.004

Cited by 24 publications

(21 citation statements)

References 133 publications

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“…Several review articles have recently summarized the function of YB-1 in various cancers [ 16 , 17 ]. In this review, we focus on newly described functions of YB-1 in cancer, encompassing its functions in the immune system and autophagy, its upstream regulation, post-translational modifications, and potential targeted strategies.…”

Section: Introductionmentioning

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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Section: Introductionmentioning

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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“…YB-1 is a multifunctional RNA-binding protein mainly involved in RNA metabolism and other processes related to the maintenance of genome stability in animals ( Mordovkina et al, 2020 ; Sangermano et al, 2020 ). Initially, YB-1 was identified as an RNA-binding protein implicated in the regulation of transcription and RNA metabolism ( Eliseeva et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the translocation of YB-1 from the cytoplasm to nucleus has been reported, mainly, upon treatment with a DNA-damaging drug; these data support the idea that YB-1 has nuclear-specific functions in cancer cells ( Stein et al, 2001 ; Fujita et al, 2005 ; Sorokin et al, 2005 ). YB-1 actions in the cytoplasm are predominantly associated with mRNA metabolism ( Budkina et al, 2020 ), while the nuclear function of YB-1—in addition to its described role as a transcription factor—remains to be elucidated ( Sangermano et al, 2020 ). The participation of YB-1 in DNA repair was recently suggested because of its interactions with damaged DNA and several repair proteins identified in in vitro studies using recombinant proteins and cells ( Hasegawa et al, 1991 ; Ise et al, 1999 ; Das et al, 2007 ; Gao et al, 2009 ; Fomina et al, 2015 ; Alemasova et al, 2016 ; Alemasova et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

The C-Terminal Domain of Y-Box Binding Protein 1 Exhibits Structure-Specific Binding to Poly(ADP-Ribose), Which Regulates PARP1 Activity

Naumenko

Sukhanova

Hamon

et al. 2022

Front. Cell Dev. Biol.

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Y-box-binding protein 1 (YB-1) is a multifunctional protein involved in the regulation of gene expression. Recent studies showed that in addition to its role in the RNA and DNA metabolism, YB-1 is involved in the regulation of PARP1 activity, which catalyzes poly(ADP-ribose) [PAR] synthesis under genotoxic stress through auto-poly(ADP-ribosyl)ation or protein trans-poly(ADP-ribosyl)ation. Nonetheless, the exact mechanism by which YB-1 regulates PAR synthesis remains to be determined. YB-1 contains a disordered Ala/Pro-rich N-terminal domain, a cold shock domain, and an intrinsically disordered C-terminal domain (CTD) carrying four clusters of positively charged amino acid residues. Here, we examined the functional role of the disordered CTD of YB-1 in PAR binding and in the regulation of PARP1-driven PAR synthesis in vitro. We demonstrated that the rate of PARP1-dependent synthesis of PAR is higher in the presence of YB-1 and is tightly controlled by the interaction between YB-1 CTD and PAR. Moreover, YB-1 acts as an effective cofactor in the PAR synthesis catalyzed by the PARP1 point mutants that generate various PAR polymeric structures, namely, short hypo- or hyperbranched polymers. We showed that either a decrease in chain length or an increase in branching frequency of PAR affect its binding affinity for YB-1 and YB-1–mediated stimulation of PARP1 enzymatic activity. These results provide important insight into the mechanism underlying the regulation of PARP1 activity by PAR-binding proteins containing disordered regions with clusters of positively charged amino acid residues, suggesting that YB-1 CTD-like domains may be considered PAR “readers” just as other known PAR-binding modules.

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“…YB-1 is a nuclear-cytoplasmic shuttling protein with functions that depend on subcellular localization. Despite the clinical significance [ 16 , 17 , 18 , 19 ], the mechanisms regulating YB-1 localization have not been studied in detail. More than 10% of YB-1 residues could be post-translationally modified.…”

Section: Discussionmentioning

confidence: 99%

“…YB-1 translocates to the nucleus at the boundary of the G1/S [ 5 ] and G2/M phases [ 7 ], upon serum, IL-1β, and IFNγ stimulation [ 8 , 9 , 10 ], transcription inhibition [ 11 , 12 , 13 ], UV irradiation [ 14 ], and under oxidative stress [ 15 ]. YB-1 is over-expressed in various human cancers and its nuclear localization is associated with the multidrug-resistant phenotype, cancer progression, and a poor prognosis (reviewed in [ 16 , 17 , 18 , 19 ]).…”

Section: Introductionmentioning

confidence: 99%

YB-1 Phosphorylation at Serine 209 Inhibits Its Nuclear Translocation

Sogorina

Kim

Sorokin

et al. 2021

IJMS

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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.

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Y box binding protein 1 (YB-1) oncoprotein at the hub of DNA proliferation, damage and cancer progression

Cited by 24 publications

References 133 publications

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

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

The C-Terminal Domain of Y-Box Binding Protein 1 Exhibits Structure-Specific Binding to Poly(ADP-Ribose), Which Regulates PARP1 Activity

YB-1 Phosphorylation at Serine 209 Inhibits Its Nuclear Translocation

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