Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chromodomain helicase/ATPase DNA-binding protein 1-like (CHD1L) gene is a novel oncogene amplified in many solid tumors. We investigated its role in breast cancer. CHD1L was over-expressed in 49.1% (57/116) breast cancer patients. Overexpression of CHD1L was significantly associated with younger age at diagnosis (P = 0.016), lymph node involvement (P = 0.040), higher tumor grade (P = 0.027), higher proliferation rate (P = 0.007) and shorter disease-free survival rate (77.2% vs. 91.5%, P = 0.037). A cDNA microarray analysis identified MDM2 as an important downstream target of CHD1L. And MDM2/p53 signaling pathway was showed to be significantly modulated by CHD1L. Further in vitro study showed that overexpression of CHD1L can promote tumorigenesis, metastasis, invasion and cell cycle progress. In vivo study confirmed the tumorigenesis ability of CHD1L. shRNA-mediated CHD1L silencing could abolishes the tumor-promotion effect of CHD1L in vitro and in vivo. In conclusion, CHD1L may promote the progress of breast cancer cells via the MDM2/p53 signaling pathway. This study identified CHD1L as a prognostic factor for breast cancer and MDM2 might be used as a potential target for therapeutic intervention in CHD1L overexpression breast cancer.
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PMID:CHD1L promotes cell cycle progression and cell motility by up-regulating MDM2 in breast cancer. 3097 84

Interactions between DNA and DNA-binding proteins play an important role in many essential cellular processes. A key function of the DNA-binding protein p53 is to search for and bind to target sites incorporated in genomic DNA, which triggers transcriptional regulation. How do p53 molecules achieve "rapid" and "accurate" target search in living cells? The search dynamics of p53 were expected to include 3D diffusion in solution, 1D diffusion along DNA, and intersegmental transfer between two different DNA strands. Single-molecule fluorescence microscopy enabled the tracking of p53 molecules on DNA and the characterization of these dynamics quantitatively. Recent intensive single-molecule studies of p53 succeeded in revealing each of these search dynamics. Here, we review these studies and discuss the target search mechanisms of p53.
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PMID:How p53 Molecules Solve the Target DNA Search Problem: A Review. 3203 63


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