共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
为了研究 C B P在胰岛 H I T 细胞中调节基因转录的机制,将不同的 C B P片段瞬时转染到细胞中,观察其转录活性.实验表明,在胰岛 H I T 细胞中,膜去极化及 c A M P 均可诱导 C B P30( C R E B结合功能区)转录活性增强,并有协同效应. P K C对 C B P30 的转录活性无影响;与 C R E B有更强结合力的 C B P K I X S/ B(氨基酸序列短于 C B P30 的 C R E B结合功能区)其基本转录活性及膜去极化、c A M P诱导下的转录活性均比 C B P30 更强.反义 C R E B 的过度表达可降低 c A M P诱导的 C B P的转录活性.提示在胰岛 H I T 细胞中,膜去极化及 c A M P对共转录因子 C B P转录活性的调节作用通过 C R E B介导. 相似文献
3.
4.
5.
6.
7.
8.
Magnitude of the CREB-dependent transcriptional response is determined by the strength of the interaction between the kinase-inducible domain of CREB and the KIX domain of CREB-binding protein 总被引:7,自引:0,他引:7
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Shaywitz AJ Dove SL Kornhauser JM Hochschild A Greenberg ME 《Molecular and cellular biology》2000,20(24):9409-9422
9.
10.
A number of second messenger pathways propagate inductive signals via protein-protein interactions that are phosphorylation-dependent. The second messenger, cAMP, for example, promotes cellular gene expression via the protein kinase A-mediated phosphorylation of cAMP-response element-binding protein (CREB) at Ser(133), and this modification in turn stimulates the association of CREB with the co-activator, CREB-binding protein (CBP). The solution structure of the CREB.CBP complex, using relevant interaction domains, kinase inducible domain and kinase-induced domain interacting domain, referred to as KID and KIX, respectively, shows that KID undergoes a coil to helix transition, upon binding to KIX, that stabilizes complex formation. Whether such changes occur in the context of the full-length CREB and CBP proteins, however, is unclear. Here we characterize a novel antiserum that specifically binds to the CREB. CBP complex but to neither protein individually. Epitope mapping experiments demonstrate that the CREB.CBP antiserum detects residues in KID that undergo a conformational change upon binding to KIX. The ability of this antiserum to recognize full-length CREB.CBP complexes in a phospho-(Ser(133))-dependent manner demonstrates that the structural transition observed with the isolated KID domain also occurs in the context of the full-length CREB protein. To our knowledge, this is the first report documenting formation of endogenous cellular protein-protein complexes in situ. 相似文献
11.
12.
13.
14.
15.
Activation of the cyclin D1 gene by the E1A-associated protein p300 through AP-1 inhibits cellular apoptosis 总被引:14,自引:0,他引:14
Albanese C D'Amico M Reutens AT Fu M Watanabe G Lee RJ Kitsis RN Henglein B Avantaggiati M Somasundaram K Thimmapaya B Pestell RG 《The Journal of biological chemistry》1999,274(48):34186-34195
The adenovirus E1A protein interferes with regulators of apoptosis and growth by physically interacting with cell cycle regulatory proteins including the retinoblastoma tumor suppressor protein and the coactivator proteins p300/CBP (where CBP is the CREB-binding protein). The p300/CBP proteins occupy a pivotal role in regulating mitogenic signaling and apoptosis. The mechanisms by which cell cycle control genes are directly regulated by p300 remain to be determined. The cyclin D1 gene, which is overexpressed in many different tumor types, encodes a regulatory subunit of a holoenzyme that phosphorylates and inactivates PRB. In the present study E1A12S inhibited the cyclin D1 promoter via the amino-terminal p300/CBP binding domain in human choriocarcinoma JEG-3 cells. p300 induced cyclin D1 protein abundance, and p300, but not CBP, induced the cyclin D1 promoter. cyclin D1 or p300 overexpression inhibited apoptosis in JEG-3 cells. The CH3 region of p300, which was required for induction of cyclin D1, was also required for the inhibition of apoptosis. p300 activated the cyclin D1 promoter through an activator protein-1 (AP-1) site at -954 and was identified within a DNA-bound complex with c-Jun at the AP-1 site. Apoptosis rates of embryonic fibroblasts derived from mice homozygously deleted of the cyclin D1 gene (cyclin D1(-/-)) were increased compared with wild type control on several distinct matrices. p300 inhibited apoptosis in cyclin D1(+/+) fibroblasts but increased apoptosis in cyclin D1(-/-) cells. The anti-apoptotic function of cyclin D1, demonstrated by sub-G(1) analysis and annexin V staining, may contribute to its cellular transforming and cooperative oncogenic properties. 相似文献
16.
17.
18.