Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We initially identified c-myc promoter-binding protein 1 (MBP-1) from a human cervical carcinoma cell expression library which negatively regulates c-myc promoter activity. A recent study demonstrated that MBP-1 acts as a general transcriptional repressor (A. K. Ghosh, R. Steele, and R. B. Ray, Mol. Cell. Biol. 19:2880-2886, 1999). In order to identify the cellular protein(s) interacting with MBP-1 for transcriptional regulation, a HeLa cell cDNA expression library was screened using a yeast two-hybrid system. An MBP-1-interacting cDNA encoding a polypeptide of 140 amino acid residues with an approximate molecular mass of 16 kDa was identified and named MBP-1 interacting protein-2A (MIP-2A). MIP-2A has a sequence similarity with an unknown mRNA and SEDL. Mutations in the SEDL gene, located at human chromosome Xp22, has recently been implicated with an X-linked genetic disease, although the function of SEDL gene product was not determined (A. K. Gedeon et al., Nat. Genet. 22:400-404, 1999). However, our results suggested the localization of MIP-2A at human chromosome 19. The specificity of interaction between MBP-1 and MIP-2A was verified by an in vitro glutathione S-transferase pulldown experiment, a mammalian two-hybrid analysis, and in vivo coimmunoprecipitation assays. Further analysis revealed that the amino-terminal domain of MBP-1 (amino acids 1 to 95) interacts with MIP-2A. Immunofluorescent staining suggested colocalization of MIP-2A and MBP-1 primarily in the perinuclear membrane of cells. Functional analysis demonstrated that MIP-2A relieves MBP-1 mediated transcriptional repression on c-myc promoter. Additionally, MIP-2A antagonizes cell growth regulatory role of MBP-1. Taken together, these results suggest the functional interaction of MIP-2A and MBP-1 in cell growth regulation.
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PMID:A novel 16-kilodalton cellular protein physically interacts with and antagonizes the functional activity of c-myc promoter-binding protein 1. 1113 51

Sedlin is an evolutionarily conserved and ubiquitously expressed protein that is encoded by the gene SEDL. Mutations in the latter are known to be causative for spondyloepiphyseal dysplasia tarda. However, the mechanism underlying this remains unclear. We have previously shown that Sedlin interacts with the intracellular chloride channel proteins CLIC1 and CLIC2 in the cytoplasm. In this report we show that Sedlin is also physically associated with protein associated with MRG 14 kDa (PAM14), a nuclear protein that interacts with the transcription factor MORF4-related gene on chromosome 15 (MRG15). This was suggested by yeast two-hybrid screening and was confirmed with GST pull-down and immunoprecipitation assays. Moreover, we demonstrate that the C-terminus of Sedlin and the N-terminus of PAM14 are critical for their interaction. Together, these results suggest that nucleus-localized Sedlin may play a role in regulation of transcriptional activities of the MRG family of transcription factors via binding to PAM14.
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PMID:Interaction of Sedlin with PAM14. 2010 51