Critical role of phosphorylation of serine 165 of YBX1 on the activation of NF-κB in colon cancer

Oncotarget
Lakshmi PrabhuTao Lu

Abstract

Y-box binding protein 1 [YBX1] is a multifunctional protein known to facilitate many of the hallmarks of cancer. Elevated levels of YBX1 protein are highly correlated with cancer progression, making it an excellent marker in cancer. The connection between YBX1 and the important nuclear factor κB [NF-κB] has never been reported. Here, we show that overexpression of wild type YBX1 [WT-YBX1] activates NF-κB, suggesting that YBX1 is a potential NF-κB activator. Furthermore, using mass spectrometry analysis we identified novel phosphorylation of serine 165 [S165] on YBX1. Overexpression of the S165A-YBX1 mutant in either HEK293 cells or colon cancer HT29 cells showed dramatically reduced NF-κB activating ability as compared with that of WT-YBX1, confirming that S165 phosphorylation is critical for the activation of NF-κB by YBX1. We also show that expression of the S165A-YBX1 mutant dramatically decreased the expression of NF-κB-inducible genes, reduced cell growth, and compromised tumorigenic ability as compared with WT-YBX1. Taken together, we provide the first evidence that YBX1 functions as a tumor promoter via NF-κB activation, and phosphorylation of S165 of YBX1 is critical for this function. Therefore, our important discovery...Continue Reading

References

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Citations

Aug 22, 2018·International Journal of Molecular Sciences·Aadhya TiwariMahmoud Toulany
Sep 29, 2020·Scientific Reports·Antja-Voy HartleyTao Lu
Jan 13, 2017·The Journal of Biological Chemistry·Matthew MartinTao Lu
Sep 28, 2018·Cell Communication and Signaling : CCS·Jonathan A Lindquist, Peter R Mertens
Apr 18, 2020·Scientific Reports·Christopher Sackmann, Martin Hallbeck
Oct 22, 2019·Frontiers in Cell and Developmental Biology·Thomas G JohnsonGlen Reid
Oct 1, 2020·International Journal of Molecular Sciences·Christopher L HessmanJonathan A Lindquist
Sep 5, 2020·Cancers·Sunali MehtaAntony Braithwaite
Apr 16, 2020·Biomolecules·Daria MordovkinaIrina Eliseeva
Feb 23, 2020·Biochemistry. Biokhimii︠a︡·K S BudkinaA V Babakov
Apr 30, 2021·Nature Communications·Marta MontesAnders H Lund
Jul 6, 2021·Cellular Signalling·Akram AlkrekshiKhalid Sossey-Alaoui
Jun 25, 2021·International Journal of Radiation Oncology, Biology, Physics·Konstanze LettauMahmoud Toulany

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Methods Mentioned

BETA
nuclear translocation
pull down
co-immunoprecipitation
PCR
transfection
coimmunoprecipitation

Software Mentioned

Prism
ImageJ
GraphPad
Oncomine
GeneNote
Mascot Science

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