The acetylation of transcription factor HBP1 by p300/CBP enhances p16INK4A expression.
The acetylation of transcription factor HBP1 by p300/CBP enhances p16INK4A expression.
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p300/CBP 对转录因子 HBP1 的乙酰化增强了 p16INK4A 的表达。
DOI：
10.1093/nar/gkr818
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发表时间：
2012-02
影响因子：
14.9
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Wang W;Pan K;Chen Y;Huang C;Zhang X
HBP1是一种序列特异性的DNA结合转录因子，具有许多重要的生物学作用。它在细胞生长和分化过程中激活或抑制某些特定基因的表达。以往的研究表明，HBP1与p16INK4A启动子结合并激活p16INK4A的表达。我们发现HDAC(组蛋白脱乙酰酶)的抑制剂曲古抑素A(TSA)以HBP1依赖的方式诱导p16INK4A的表达。这一结果是通过检测带有HBP1结合位点的p16INK4A启动子与野生型p16INK4A启动子瞬时共转染HEK293T细胞和2BS细胞的相对荧光素酶活性的反式激活实验得出的。免疫沉淀法证实TSA处理后HBP1乙酰化。我们的数据表明HBP1与组蛋白乙酰转移酶p300和CREB结合蛋白(CBP)相互作用，并将p300/CBP招募到p16INK4A启动子。HBP1被p300/CBP乙酰化在两个区域：阻遏结构域(K297/305/307)和P结构域(K171/419)。HBP1在p16INK4A上的反式激活不需要抑制结构域的乙酰化。然而，荧光素酶分析和Western blotting结果表明，P结构域的乙酰化，特别是K419的乙酰化是HBP1反式激活p16INK4A所必需的。SA-β-Gal染色显示，HBP1在K419位的乙酰化增强了HBP1诱导的2BS细胞的早衰。此外，HDAC4通过永久去乙酰化HBP1抑制HBP1诱导的早衰。我们的研究结果表明，HBP1在K419位的乙酰化在HBP1诱导的p16INK4A表达中起重要作用。
HBP1 is a sequence-specific DNA-binding transcription factor with many important biological roles. It activates or represses the expression of some specific genes during cell growth and differentiation. Previous studies have exhibited that HBP1 binds to p16INK4A promoter and activates p16INK4A expression. We found that trichostatin A (TSA), an inhibitor of HDAC (histone deacetylase), induces p16INK4A expression in an HBP1-dependent manner. This result was drawn from a transactivation experiment by measuring relative luciferase activities of p16INK4A promoter with HBP1-binding site in comparison with that of the wild-type p16INK4A promoter by transient cotransfection with HBP1 into HEK293T cells and 2BS cells. HBP1 acetylation after TSA treatment was confirmed by immunoprecipitation assay. Our data showed that HBP1 interacted with histone acetyltransferase p300 and CREB-binding protein (CBP) and also recruited p300/CBP to p16INK4A promoter. HBP1 was acetylated by p300/CBP in two regions: repression domain (K297/305/307) and P domain (K171/419). Acetylation of Repression domain was not required for HBP1 transactivation on p16INK4A. However, luciferase assay and western blotting results indicate that acetylation of P domain, especially K419 acetylation is essential for HBP1 transactivation on p16INK4A. As assayed by SA-beta-gal staining, the acetylation of HBP1 at K419 enhanced HBP1-induced premature senescence in 2BS cells. In addition, HDAC4 repressed HBP1-induced premature senescence through permanently deacetylating HBP1. We conclude that our data suggest that HBP1 acetylation at K419 plays an important role in HBP1-induced p16INK4A expression.
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影响因子：
4.8
作者：
Lee, Minnkyong;Partridge, Nicola C.
通讯作者：
Partridge, Nicola C.
影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
5.3
作者：
Shih, HH;Xiu, M;Yee, AS
通讯作者：
Yee, AS
影响因子：
10.5
作者：
Tevosian, SG;Shih, HH;Yee, AS
通讯作者：
Yee, AS