YY1 restrained cell senescence through repressing the transcription of p16

Wang, Xiuli; Feng, Yunpeng; Xu, Liang; Chen, Yuli; Zhang, Yu; Su, Dongmei; Ren, Guoling; Lü, Jun; Huang, Baiqu

doi:10.1016/j.bbamcr.2008.05.015

Cited by 42 publications

(30 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, YY1 expression can similarly regulate cell growth by interaction with Rb [8], [12], [44]. YY1 can also impact senescence by regulating p16 INK4a [45], and can increase HoxB7 expression directly involved in tumor progression [46].…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of PcG Protein YY1 Negatively Regulates B Cell Development while Allowing Accumulation of Myeloid Cells and LT-HSC Cells

et al. 2012

View full text Add to dashboard Cite

Ying Yang 1 (YY1) is a multifunctional Polycomb Group (PcG) transcription factor that binds to multiple enhancer binding sites in the immunoglobulin (Ig) loci and plays vital roles in early B cell development. PcG proteins have important functions in hematopoietic stem cell renewal and YY1 is the only mammalian PcG protein with DNA binding specificity. Conditional knock-out of YY1 in the mouse B cell lineage results in arrest at the pro-B cell stage, and dosage effects have been observed at various YY1 expression levels. To investigate the impact of elevated YY1 expression on hematopoetic development, we utilized a mouse in vivo bone marrow reconstitution system. We found that mouse bone marrow cells expressing elevated levels of YY1 exhibited a selective disadvantage as they progressed from hematopoietic stem/progenitor cells to pro-B, pre-B, immature B and re-circulating B cell stages, but no disadvantage of YY1 over-expression was observed in myeloid lineage cells. Furthermore, mouse bone marrow cells expressing elevated levels of YY1 displayed enrichment for cells with surface markers characteristic of long-term hematopoietic stem cells (HSC). YY1 expression induced apoptosis in mouse B cell lines in vitro, and resulted in down-regulated expression of anti-apoptotic genes Bcl-xl and NFκB2, while no impact was observed in a mouse myeloid line. B cell apoptosis and LT-HSC enrichment induced by YY1 suggest that novel strategies to induce YY1 expression could have beneficial effects in the treatment of B lineage malignancies while preserving normal HSCs.

show abstract

Section: Discussionmentioning

confidence: 99%

Increased Expression of PcG Protein YY1 Negatively Regulates B Cell Development while Allowing Accumulation of Myeloid Cells and LT-HSC Cells

et al. 2012

View full text Add to dashboard Cite

show abstract

“…It has been demonstrated that various transcription factors, such as Ets and Bmi1, play critical roles in the transcriptional regulation p16 gene5. Our earlier studies showed that the histone acetyltransferase p300 recruited by Sp1 stimulated p16 transcription through inducing the H4 hyperacetylation on p16 gene, whereas HDAC3/4 inhibited the p16 promoter activity via the transcription factors YY1 and ZBP-89678.…”

mentioning

confidence: 96%

The interplay between p16 serine phosphorylation and arginine methylation determines its function in modulating cellular apoptosis and senescence

Yang

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

Cyclin-dependent kinase inhibitor p16INK4a (p16) primarily functions as a negative regulator of the retinoblastoma protein (Rb) -E2F pathway, thus plays critical role in cell cycle progression, cellular senescence and apoptosis. In this study, we showed that the methylation of Arg 138 and the phosphorylation of Ser 140 on p16 were critical for the control of cell proliferation and apoptosis. Compared to wild type p16, mutant p16R138K possessed improved function in preventing cell proliferation and inducing apoptosis, while the Ser 140 mutation (p16S140A) exhibited the opposite alteration. We also demonstrated that H2O2 was able to induce the phosphorylation of p16, which facilitated the interaction between CDK4 (Cyclin-dependent protein kinase) and p16, in 293T (human emborynic kidney) cells. Furthermore, the elevated arginine methylation in p16S140A mutant and increased serine phosphorylation in p16R138K mutant suggest that a antagonizing mechanism coordinating Arg 138 methylation and Ser 140 phosphorylation to regulates p16 function as well as cellular apoptosis and senescence. These findings will therefore contribute to therapeutic treatment for p16-related gene therapy by providing theoretical and experimental evidence.

show abstract

“…YY1 exerts its effects on genes involved in these processes via its ability to initiate, activate, or repress transcription depending upon the context or recruited cofactors in which it binds [15,16]. One such family of cofactors are the histone deacetylases which have been shown to bind YY1 and repress transcription when targeted to promoters [17]. YY1 has been shown to interact with p300, PCAF and CBP, all which posses the histone acetyltransferase (HAT) activity [17].…”

Section: Introductionmentioning

confidence: 99%

“…One such family of cofactors are the histone deacetylases which have been shown to bind YY1 and repress transcription when targeted to promoters [17]. YY1 has been shown to interact with p300, PCAF and CBP, all which posses the histone acetyltransferase (HAT) activity [17]. YY1 may thus activate transcription by its recruitment of HAT proteins and repress transcription by recruiting HDACs.…”

Section: Introductionmentioning

confidence: 99%

Yin Yang 1 regulates the transcriptional repression of survivin

Galloway

Osterman

Reiber

et al. 2014

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

The mechanisms for regulation of the Inhibitor of Apoptosis (IAP) Survivin in cells undergoing stress associated with tumor development and the tumor microenvironment are not well understood. The stress response transcription factors HIF-1α and Yin Yang 1 (YY1) were hypothesized to contribute to the upregulation of Survivin in tumor cells. As expected, U2OS cells overexpressing HIF-1α showed a 2- to 3-fold transactivation when transfected. Surprisingly, when YY1 was overexpressed in this survivin promoter reporter system, luciferase expression was repressed 30- to 40-fold. YY1 involvement in survivin promoter repression was confirmed using siRNA directed against YY1. These studies showed that knockdown of YY1 releases the survivin promoter from the observed repression and leads to a 3- to 5-fold increase in promoter activity above basal levels. A U2OS cell line containing a stable YY1 Tet-off system was used to determine whether a temporal increase in YY1 expression affects Survivin protein levels. A low to moderate decrease in Survivin protein was observed 24 h and 48 h after Tet removal. Studies also confirmed that YY1 is capable of directly binding to the survivin promoter. Collectively, these findings identify novel basal transcriptional requirements of survivin gene expression which are likely to play important roles in the development of cancer and resistance to its treatment.

show abstract

YY1 restrained cell senescence through repressing the transcription of p16

Cited by 42 publications

References 36 publications

Increased Expression of PcG Protein YY1 Negatively Regulates B Cell Development while Allowing Accumulation of Myeloid Cells and LT-HSC Cells

Increased Expression of PcG Protein YY1 Negatively Regulates B Cell Development while Allowing Accumulation of Myeloid Cells and LT-HSC Cells

The interplay between p16 serine phosphorylation and arginine methylation determines its function in modulating cellular apoptosis and senescence

Yin Yang 1 regulates the transcriptional repression of survivin

Contact Info

Product

Resources

About