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)

DDB2, a gene mutated in XPE patients, is involved in global genomic repair especially the repair of cyclobutane pyrimidine dimers (CPDs), and is regulated by p53 in human cells. We show that DDB2 is expressed in mouse tissues and demonstrate, using primary mouse epithelial cells, that mouse DDB2 is regulated by E2F transcription factors. Retinoblastoma (Rb), a tumor suppressor critical for the control of cell cycle progression, regulates E2F activity. Using Cre-Lox technology to delete Rb in primary mouse hepatocytes, we show that DDB2 gene expression increases, leading to elevated DDB2 protein levels. Furthermore, we show that endogenous E2F1 and E2F3 bind to DDB2 promoter and that treatment with E2F1-antisense or E2F1-small interfering RNA (siRNA) decreases DDB2 transcription, demonstrating that E2F1 is a transcriptional regulator for DDB2. This has consequences for global genomic repair: in Rb-null cells, where E2F activity is elevated, global DNA repair is increased and removal of CPDs is more efficient than in wild-type cells. Treatment with DDB2-siRNA decreases DDB2 expression and abolishes the repair phenotype of Rb-null cells. In summary, these results identify a new regulatory pathway for DDB2 by E2F, which does not require but is potentiated by p53, and demonstrate that DDB2 is involved in global repair in mouse epithelial cells.
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PMID:E2F regulates DDB2: consequences for DNA repair in Rb-deficient cells. 1717 70

Xeroderma pigmentosum (XP) is a group of rare inherited human neurocutaneous diseases, and the group C (XPC) is the major group of patients with XP in Europe, North America, and South America. Current molecular diagnostic methods for XP require specialized, expensive, and time-consuming UV sensitivity and DNA repair assays followed by gene sequencing. To determine whether immunohistochemistry (IHC) would be a robust alternative method to diagnose patients with XPC, we stained sections of paraffin-embedded skin biopsies for XPC by IHC, using 69 archived blocks from confirmed or clinically suspect patients with XPA, XPC, XPD, XPE, and without XP. We found that XPC expression was strong in all skin biopsies from patients without (14 of 14) and other patients with XP (4 of 4), whereas XPC expression was lost in all biopsies from confirmed XPC patients (29 of 29). Patches of strong XPC signal could be detected in sun-damaged skin, squamous and basal cell carcinomas from patients with XPC that colocalized with strong expression of p53 and Ki-67. Patients with XPC can therefore be diagnosed by IHC from paraffin-embedded skin biopsies from regions of skin that are without sun damage or sun-induced tumors. IHC is therefore a robust alternative method to diagnose patients with XPC. This fast and inexpensive method should increase the options for the diagnosis of patients with XPC from paraffin-embedded skin biopsies and could be developed for other complementation groups.
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PMID:Diagnosing xeroderma pigmentosum group C by immunohistochemistry. 1991 53


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