p73 competes with co-activators and recruits histone deacetylase to NF-Y in the repression of PDGF β-receptor

Uramoto, Hidetaka; Wetterskog, Daniel; Hackzell, Anders; Matsumoto, Yoshiki; Funa, Keiko

doi:10.1242/jcs.01384

Cited by 28 publications

(31 citation statements)

References 25 publications

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“…HDAC1 has been reported to interact with various transcription factors to repress specific genes. NF-Y has been shown to be associated with HDAC1 and the association is mediated by other proteins such as p73 (45). In this study, we showed that the interaction between HDAC1 and NF-Y is enhanced by RFP in transformed cells.…”

Section: Discussionsupporting

confidence: 50%

Characterization of the HDAC1 Complex That Regulates the Sensitivity of Cancer Cells to Oxidative Stress

Kato¹,

Shimono²,

Hasegawa

et al. 2009

Cancer Research

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Histone deacetylases (HDAC) are involved in carcinogenesis through their regulation of cell proliferation, differentiation, and survival. The inhibitors of HDAC exhibit profound synergistic effects in cancer treatment when combined with other anticancer drugs. However, the molecular mechanisms underlying this synergy are not fully understood. Here, we show that HDAC1 increases the resistance of cancer cells to oxidative stress by negatively regulating the expression of thioredoxin binding protein 2 (TBP-2). We found that the recruitment of HDAC1 to the TBP-2 promoter is mediated by a protein complex consisting of RET finger protein (RFP; also called TRIM27) and the trimeric transcription factor NF-Y. Accordingly, RNA interference-mediated depletion of RFP led to the disruption of the protein complex and a marked increase in the sensitivity of cancer cells to cisplatin, a potent inducer of oxidative stress. Furthermore, high levels of RFP expression correlated with down-regulation of TBP-2 in human colon cancers and were associated with poor clinical outcome. These findings reveal the diverse cancer-promoting activities of HDAC1 and identify RFP as a key regulator that provides cancer cells with resistance to anticancer drugs.

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Section: Discussionsupporting

confidence: 50%

Characterization of the HDAC1 Complex That Regulates the Sensitivity of Cancer Cells to Oxidative Stress

Kato¹,

Shimono²,

Hasegawa

et al. 2009

Cancer Research

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show abstract

“…Several transcription factors (TFs) are known to activate or repress Pdgfrb in cell culture systems; however, the biological function of Pdgfrb regulation by these TFs in vivo remains elusive (Ballagi et al, 1995;Uramoto et al, 2004;Jin et al, 2008;Weissmueller et al, 2014). In the present study, we show Koss et al, 2012) and the osteoblast-related gene Osx (Sp7 -Mouse Genome Informatics) (Gordon et al, 2010).…”

Section: Discussionmentioning

confidence: 59%

Pbx1 dependent control of VMC differentiation kinetics underlies gross renal vascular patterning

et al. 2015

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The architecture of an organ's vascular bed subserves its physiological function and metabolic demands. However, the mechanisms underlying gross vascular patterning remain elusive. Using intravital dye labeling and 3D imaging, we discovered that systems-level vascular patterning in the kidney is dependent on the kinetics of vascular mural cell (VMC) differentiation. Conditional ablation of the TALE transcription factor Pbx1 in renal VMC progenitors in the mouse led to the premature upregulation of PDGFRβ, a master initiator of VMC-blood vessel association. This precocious VMC differentiation resulted in nonproductive angiogenesis, abnormal renal arterial tree patterning and neonatal death consistent with kidney dysfunction. Notably, we establish that Pbx1 directly represses Pdgfrb, and demonstrate that decreased Pdgfrb dosage in conditional Pbx1 mutants substantially rescues vascular patterning defects and neonatal survival. These findings identify, for the first time, an in vivo transcriptional regulator of PDGFRβ, and reveal a previously unappreciated role for VMCs in systems-level vascular patterning.

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“…In nonstressed cells, NF-Y is present on the Grp78 promoter and may play a role in suppressing its activity through interactions with transcriptional repressors (44,53). The presence of a high-affinity NF-Y binding site has previously been shown to be necessary for ATF6-mediated induction of the Grp78 promoter (24), and it may also attract other coactivators and chromatin modifiers to the promoter, resulting in activation (5).…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic Reticulum Stress Induction of the Grp78/BiP Promoter: Activating Mechanisms Mediated by YY1 and Its Interactive Chromatin Modifiers

et al. 2005

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The unfolded protein response is an evolutionarily conserved mechanism whereby cells respond to stress conditions that target the endoplasmic reticulum (ER). The transcriptional activation of the promoter of GRP78/BiP, a prosurvival ER chaperone, has been used extensively as an indicator of the onset of the UPR. YY1, a constitutively expressed multifunctional transcription factor, activates the Grp78 promoter only under ER stress conditions. Previously, in vivo footprinting analysis revealed that the YY1 binding site of the ER stress response element of the Grp78 promoter exhibits ER stress-induced changes in occupancy. Toward understanding the underlying mechanisms of these unique phenomena, we performed chromatin immunoprecipitation analyses, revealing that YY1 only occupies the Grp78 promoter upon ER stress and is mediated in part by the nuclear form of ATF6. We show that YY1 is an essential coactivator of ATF6 and uncover their specific interactive domains. Using small interfering RNA against YY1 and insertional mutation of the gene encoding ATF6␣, we provide direct evidence that YY1 and ATF6 are required for optimal stress induction of Grp78. We also discovered enhancement of the ER-stressed induction of the Grp78 promoter through the interaction of YY1 with the arginine methyltransferase PRMT1 and evidence of its action through methylation of the arginine 3 residue on histone H4. Furthermore, we detected ER stress-induced binding of the histone acetyltransferase p300 to the Grp78 promoter and histone H4 acetylation. A model for the ER stress-mediated transcription factor binding and chromatin modifications at the Grp78 promoter leading to its activation is proposed.

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p73 competes with co-activators and recruits histone deacetylase to NF-Y in the repression of PDGF β-receptor

Cited by 28 publications

References 25 publications

Characterization of the HDAC1 Complex That Regulates the Sensitivity of Cancer Cells to Oxidative Stress

Characterization of the HDAC1 Complex That Regulates the Sensitivity of Cancer Cells to Oxidative Stress

Pbx1 dependent control of VMC differentiation kinetics underlies gross renal vascular patterning

Endoplasmic Reticulum Stress Induction of the Grp78/BiP Promoter: Activating Mechanisms Mediated by YY1 and Its Interactive Chromatin Modifiers

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