p73 independent of c-Myc represses transcription of platelet-derived growth factor β-receptor through interaction with NF-Y
p73 independent of c-Myc represses transcription of platelet-derived growth factor β-receptor through interaction with NF-Y
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DOI：
10.1074/jbc.m204483200
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发表时间：
2002-10-18
影响因子：
4.8
通讯作者：
Funa, K
中科院分区：
文献类型：
--
作者：
Hackzell, A;Uramoto, H;Funa, K
我们最近报道了c-Myc抑制血小板衍生生长因子（PDGF）β受体的转录（Izumi，H.，莫兰德角，佩恩湖Z.，Ishisaki，A.，Kohno，K.，和Funa，K.等人（2001）J. Cell Sci. 114，15331544）。我们在这里证明，p53家族蛋白p73 α抑制PDGF β受体转录基本上由相同的机制。p73 α而不是p73，6或p53抑制转录，这与其结合NF-YC和NF-YB的能力一致。除p63 α外，其他p73亚型（即p73 β、p73 γ、p73是的元件）、p73 α的C-末端缺失突变体和p53均不能结合NF-γ。这一发现表明仅存在于p73 α和p63 α中的不育α基序结构域是相互作用位点。对于抑制，p73 α的N-末端反式激活结构域也是不可或缺的，这证明了p73 α活性在该机制中的重要性。p73 α结合NF-YC的C-末端HAP结构域，先前发现该结构域是与c-Myc和TBP的相互作用位点。因为c-Myc诱导并激活p73 α（Zaika，A.，欧文，M.，桑塞姆角，和Moll，U. M.（2001）J.Biol.Chem.276，11310-11316），并且它们彼此结合（Uramoto，H.，Izumi，H.，伊势，T.，多田，M.，内海，T.，Kuwano，M.，Yasumoto，K.，Funa，K.，和Kohno，K.（2002）J.Biol.Chem.277，出版中），我们检测了p73的抑制是否依赖于c-Myc。然而，Myc-null大鼠成纤维细胞也易受p73 α诱导的抑制。NIH 3 T3细胞的血清刺激逐渐减少了与PDGF β受体启动子结合的内源性NF-Y的量，而核提取物中的NF-YA表达保持不变。我们的研究结果表明，血清刺激诱导c-Myc和p73 α，通过抑制其转录导致PDGF β受体表达下调。
We recently reported that c-Myc represses the transcription of platelet-derived growth factor (PDGF) beta-receptor (Izumi, H., Molander, C., Penn, L. Z., Ishisaki, A., Kohno, K., and Funa, K. (2001) J. Cell Sci. 114, 15331544). We demonstrate here that the p53 family protein p73alpha represses PDGF beta-receptor transcription essentially by the same mechanism. p73alpha but not p73,6 or p53 represses the transcription in concordance with its ability to bind NF-YC and NF-YB. None of other p73 isoforms (i.e. p73beta, p73gamma, p73is an element of), C-terminal deletion mutants of p73alpha, and p53 is able to bind NF-Y with the exception of p63alpha. This finding suggests that the sterile alpha-motif domain present only in p73alpha and p63alpha is the interaction site. For the repression, the N-terminal transactivation domain of p73alpha is also indispensable, arguing for the importance of the activity of p73alpha in the mechanism. p73alpha binds the C-terminal HAP domain of NF-YC previously found to be the interaction site with c-Myc and TBP. Because c-Myc induces and activates p73alpha (Zaika, A., Irwin, M., Sansome, C., and Moll, U. M. (2001) J. Biol. Chem. 276, 11310-11316) and they bind each other (Uramoto, H., Izumi, H., Ise, T., Tada, M., Uchiumi, T., Kuwano, M., Yasumoto, K., Funa, K., and Kohno, K. (2002) J. Biol. Chem. 277, in press), we examined whether the repression by p73 is dependent on c-Myc. However, Myc-null rat fibroblasts are also susceptible to p73alpha-induced repression. Serum stimulation of NIH3T3 cells gradually decreased the amount of endogenous NF-Y binding to the PDGF beta-receptor promoter, whereas NF-YA expression in the nuclear extracts remains unchanged. Our results indicate that serum stimulation induces c-Myc and p73alpha, leading to the downregulation of PDGF beta-receptor expression by repressing its transcription.