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Article
Crystal structure at 1.7 Å of the bovine papillomavirus-1 E2 DMA-binding domain bound to its DNA target
The dominant transcriptional regulator of the papiIlomaviruses, E2, binds to its specific DNA target through a previously unobserved dimeric ant i para I lei β-barrel. The DNA is severely but smoothly bent ove...
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Article
Binding and modulation of p53 by p300/CBP coactivators
The adenovirus E1A and SV40 large-T-antigen oncoproteins bind to members of the p300/CBP transcriptional coactivator family. Binding of p300/CBP is implicated in the transforming mechanisms of E1A and T-antige...
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Article
A post-ubiquitination role for MDM2 and hHR23A in the p53 degradation pathway
Abrogation of ubiquitin/proteasome-dependent turnover of p53 is critical for its activation. UbL-UBA proteins, including human homolog of Rad23 (hHR23) proteins, may regulate proteasomal degradation of substra...
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Protocol
p53 Ubiquitination and Proteasomal Degradation
p53 levels and activity are controlled in large part through regulated ubiquitination and subsequent destruction by the 26S proteasome. Monoubiquitination of p53 is mediated primarily by the RING-finger E3 ubi...
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Chapter
Mechanisms of Mutant p53 Stabilization in Cancer
p53 transactivates cell cycle inhibitory, apoptosis or senescence-related genes in response to DNA damage to protect the genetic integrity of the cell. Highlighting its critical tumor suppressor functions, p53...
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Article
Open AccessCtBP—a targetable dependency for tumor-initiating cell activity and metastasis in pancreatic adenocarcinoma
Ctbp2 is a uniquely targetable oncogenic transcriptional coregulator, exhibiting overexpression in most common solid tumors, and critical to the tumor-initiating cell (TIC) transcriptional program. In the “CKP” m...
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Article
Open AccessCtBP determines ovarian cancer cell fate through repression of death receptors
C-terminal binding protein 2 (CtBP2) is elevated in epithelial ovarian cancer, especially in the aggressive and highly lethal subtype, high-grade serous ovarian cancer (HGSOC). However, whether HGSOC tumor pro...
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Article
Open AccessThe oncogenicity of tumor-derived mutant p53 is enhanced by the recruitment of PLK3
p53 mutations with single amino acid changes in cancer often lead to dominant oncogenic changes. Here, we have developed a mouse model of gain-of-function (GOF) p53-driven lung cancer utilizing conditionally a...
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Article
Open AccessCoordinate transcriptional regulation of ErbB2/3 by C-terminal binding protein 2 signals sensitivity to ErbB2 inhibition in pancreatic adenocarcinoma
There is a critical need to identify new therapeutic vulnerabilities in pancreatic ductal adenocarcinoma (PDAC). Transcriptional co-regulators C-terminal binding proteins (CtBP) 1 and 2 are highly overexpresse...