Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gossypol, a secondary metabolite stored in the glands of cotton, protecting cottonseed from consumption of human and monogastric animal. This ability is unique to the tribe Gossypieae. Although the relationship between gossypol and pigment gland has been studied for a long time, the development mechanism of pigment gland has not been investigated at molecular level. Here we described a simple and efficient method for constructing a normalized cDNA library from a cotton mutant, Xiangmian-18, during its pigments gland forming stage. It combined switching mechanism at 5'-end of RNA transcript (SMART) technique and duplex-specific nuclease (DSN) normalization methods. In a model experiment, double-stranded cDNAs were synthesized from mRNAs, processed by normalization and Sfi I restriction endonuclease, and finally the cDNAs were ligated to pDNR-LIB vector. The ligation mixture was transformed into E. coli JM109 by electroporation. Counting the number of colonies, the titer of the original library was 5.86x10(5)cfu/ml in this library. Electrophoresis gel results indicated the fragments ranged from 800bp to 2kb, with the average size of 1400bp. Random picking clones showed that the recombination rate was 94%. The results showed that the cDNA library constructed successfully was a full-length library with high quality, and could be used to screen the genes related to development of pigments gland cottons.
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PMID:Construction of cDNA library of cotton mutant Xiangmian-18 library during gland forming stage. 1768 35

The human apurinic/apyrimidinic endonuclease 1/redox enhancing factor-1 (APE1/Ref-1), an essential multifunctional protein involved in the repair of oxidative deoxyribonucleic acid (DNA) damage and transcriptional regulation, is often overexpressed in tumor tissues and cancer cells. Moreover, APE1/Ref-1 (APE1) overexpression has been linked to chemoresistance in human tumors. Thus, inhibiting APE1 function in cancer cells is considered a promising strategy to overcome resistance to therapeutic agents. Gossypol is a Bcl-2 homology 3 (BH3)-mimetic agent and is able to bind to the BH3 domain of B-cell lymphoma 2 (Bcl-2) family members. Other studies demonstrated that Bcl-2 directly interacted with APE1 via its BH domains. Using apurinic/apyrimidinic (AP) endonuclease assays, we found that gossypol inhibits the repair activity of APE1. Electrophoretic mobility shift assays and dual luciferase assays showed that gossypol could also inhibit the redox function of APE1. Using dual polarization interferometry technology, we show that gossypol can directly interact with APE1. Furthermore, addition of gossypol, in conjunction with APE1 overexpression, leads to cancer cell death. The addition of gossypol also enhances the cell killing effect of the laboratory alkylating agent methyl methanesulfonate and the clinical agent cisplatin (DDP). Administration of gossypol significantly inhibited the growth of xenografts. Furthermore, the combined treatment of gossypol and DDP resulted in a statistically higher antitumor activity compared with DDP alone in vivo. In conclusion, we have demonstrated that gossypol effectively inhibits the repair and redox activity of APE1 through a direct interaction.
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PMID:Identification of a novel potential antitumor activity of gossypol as an APE1/Ref-1 inhibitor. 2487 79