YB-1 transcription in the postnatal brain is regulated by a bHLH transcription factor Math2 through an E-box sequence in the 5′-UTR of the gene

Ohashi, Sachiyo; Fukumura, Reiko; Higuchi, Takashi; Kobayashi, Shunsuke

doi:10.1007/s11010-009-0065-x

Cited by 11 publications

(5 citation statements)

References 30 publications

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“…We have reported that YB-1 transcription in the postnatal brain is regulated by a transcription factor, Math2 (Ohashi et al 2009b). This indicates that a high level of YB-1 is supplied to the cytoplasm of neurons in the developing brain to regulate the synthesis of proteins such as GluR2 and CaM1, thereafter declining to a much lower level that may be sufficient to maintain the established nervous system.…”

Section: Discussionmentioning

confidence: 99%

YB-1 Binds to GluR2 mRNA and CaM1 mRNA in the Brain and Regulates their Translational Levels in an Activity-Dependent Manner

et al. 2010

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The translational regulator YB-1 binds to mRNAs. In the brain, YB-1 is prominently expressed from the prenatal stage until the first week after birth, being associated with polysomes and distributed in neuronal dendrites, but its expression declines to a much lower level thereafter. It is therefore of interest to identify the mRNAs whose translation is controlled by YB-1 in the postnatal growing brain. In this study we found that YB-1 interacted with the mRNAs for glutamate receptor subunit 2 (GluR2) and calmodulin1 (CaM1) in both brain and NG108-15 cells. Overexpression or knockdown of YB-1 altered the levels of these proteins significantly in cultured cells without any change in their mRNA levels. When the cells were treated with neurotransmitters, translation of these proteins was induced within a short time, and a change in the amount of YB-1 on its target mRNAs was observed in the heavy-sedimenting polysome fractions on a sucrose gradient. Depletion of YB-1 expression by siRNA abrogated the translational activation. Furthermore, in the brain of kainic acid-treated mice, the distribution of YB-1 was shifted to much heavier fractions associated with polysomes within 30 min to 1 h after the treatment, and the distribution returned to lighter fractions within the following 2 h. The protein levels of GluR2 and CaM1 were also increased transiently when the distribution of YB-1 on the gradient changed. These results suggest that in the brain of growing mice, YB-1 binds to GluR2 and CaM1 mRNAs and regulates their translation in an activity-dependent manner.

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Section: Discussionmentioning

confidence: 99%

YB-1 Binds to GluR2 mRNA and CaM1 mRNA in the Brain and Regulates their Translational Levels in an Activity-Dependent Manner

et al. 2010

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“…Since YB-1 performs many functions in the cell and participates in its crucial events, synthesis of this protein must be under strict control. There are reports that the following transcription factors are involved in regulation of transcription of the YB-1 gene: Twist, 36 GATA, 37 Math2 (Neurod6), 38 p73, c-Myc и Max. 39 A few studies have been reported on regulation of YB-1 synthesis at the posttranscriptional level.…”

Section: Discussionmentioning

confidence: 99%

Interplay between Y-box-binding protein 1 (YB-1) and poly(A) binding protein (PABP) in specific regulation ofYB-1mRNA translation

et al. 2011

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YB-1 is a DNA- and RNA-binding protein that regulates expression of many important genes. Its deficiency or excess may pose threats, including malignant cellular transformation and metastasis, which explains the necessity of strict control over its amount at every level. As we showed previously, the 3' untranslated region (UTR) of YB-1 mRNA contains a regulatory element specifically binding to YB-1 and PABP (PABPC1). Also, we showed that YB-1 selectively inhibits YB-1 mRNA translation, while PABP stimulates it in a poly(A) tail-independent manner. It was suggested that regulation of YB-1 mRNA translation involves competition between PABP and YB-1 for binding to the regulatory element. Here we offer cogent evidence for this model and add novel details to the mechanism of regulation of YB-1 synthesis. In experiments on regulatory element deletion we showed that it is this element that is responsible for a specific effect of YB-1 and PABP on YB-1 mRNA translation. Mutations eliminating only specific YB-1 affinity for this element suppressed the inhibitory effect of YB-1 and concurrently dramatically decreased the PABP stimulating effect. Mutations reducing only specific PABP affinity for this element, as well as spatial separation of the YB-1- and PABP binding sites, did not affect the YB-1 inhibitory action but completely abolished the positive PABP effect. Together, these results unambiguously prove direct inhibitory action of YB-1 on its mRNA translation, while the positive effect of PABP is realized through displacing YB-1 from the regulatory element.

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“…Loss of YB-1 is embryonically lethal for mice where major developmental defects were reported in the brain (6,7), yet the molecular mechanism underlying this is unknown. Although it is downregulated at postnatal life (8), it is highly expressed in cancer where its expression is associated with poor prognosis (4). YB-1 was highly expressed in gliomas when compared with surrounding normal brain tissues (9).…”

Section: Introductionmentioning

confidence: 99%

YB-1 Bridges Neural Stem Cells and Brain Tumor–Initiating Cells via Its Roles in Differentiation and Cell Growth

et al. 2011

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The Y-box binding protein 1 (YB-1) is upregulated in many human malignancies including glioblastoma (GBM). It is also essential for normal brain development, suggesting that YB-1 is part of a neural stem cell (NSC) network. Here, we show that YB-1 was highly expressed in the subventricular zone (SVZ) of mouse fetal brain tissues but not in terminally differentiated primary astrocytes. Conversely, YB-1 knockout mice had reduced Sox-2, nestin, and musashi-1 expression in the SVZ. Although primary murine neurospheres were rich in YB-1, its expression was lost during glial differentiation. Glial tumors often express NSC markers and tend to loose the cellular control that governs differentiation; therefore, we addressed whether YB-1 served a similar role in cancer cells. YB-1, Sox-2, musashi-1, Bmi-1, and nestin are coordinately expressed in SF188 cells and 9/9 GBM patientderived primary brain tumor-initiating cells (BTIC). Silencing YB-1 with siRNA attenuated the expression of these NSC markers, reduced neurosphere growth, and triggered differentiation via coordinate loss of GSK3-b. Furthermore, differentiation of BTIC with 1% serum or bone morphogenetic protein-4 suppressed YB-1 protein expression. Likewise, YB-1 expression was lost during differentiation of normal human NSCs. Consistent with these observations, YB-1 expression increased with tumor grade (n ¼ 49 cases). YB-1 was also coexpressed with Bmi-1 (Spearmans 0.80, P > 0.001) and Sox-2 (Spearmans 0.66, P > 0.001) based on the analysis of 282 cases of high-grade gliomas. These proteins were highly expressed in 10/15 (67%) of GBM patients that subsequently relapsed. In conclusion, YB-1 correlatively expresses with NSC markers where it functions to promote cell growth and inhibit differentiation. Cancer Res; 71(16); 5569-78. Ó2011 AACR.

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YB-1 transcription in the postnatal brain is regulated by a bHLH transcription factor Math2 through an E-box sequence in the 5′-UTR of the gene

Cited by 11 publications

References 30 publications

YB-1 Binds to GluR2 mRNA and CaM1 mRNA in the Brain and Regulates their Translational Levels in an Activity-Dependent Manner

YB-1 Binds to GluR2 mRNA and CaM1 mRNA in the Brain and Regulates their Translational Levels in an Activity-Dependent Manner

Interplay between Y-box-binding protein 1 (YB-1) and poly(A) binding protein (PABP) in specific regulation ofYB-1mRNA translation

YB-1 Bridges Neural Stem Cells and Brain Tumor–Initiating Cells via Its Roles in Differentiation and Cell Growth

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