Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We recently identified the existence of a novel interaction between heat shock transcription factor 2 (HSF2) and the PR65/A subunit of protein phosphatase 2A (PP2A) and showed that HSF2 is able to compete with the PP2A catalytic subunit for binding to PR65. To elucidate the mechanistic basis of this competition between HSF2 and catalytic subunit at the molecular level we have sought to characterize sequences within PR65 that are important for interaction with HSF2. The results identify the intra-repeat loop within HEAT repeat 11 of PR65 as critical for interaction with HSF2. Analysis of point mutants within this loop region of PR65 identify lysine 416 as a residue critical for interaction with HSF2. Interestingly, this same lysine residue of PR65 is important for its binding to catalytic subunit. These results suggest that HSF2's ability to interfere with catalytic subunit binding to PR65 is due to competition between HSF2 and catalytic subunit for at least one amino acid residue of PR65, lysine 416. These data support the hypothesis that HSF2 represents a new type of PP2A regulatory protein.
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PMID:Molecular basis of competition between HSF2 and catalytic subunit for binding to the PR65/A subunit of PP2A. 1087 7

Previous work in our laboratory demonstrated the existence of an association between heat shock transcription factor 2 (HSF2) and the serine/threonine phosphatase 2A, which is mediated by interaction between HSF2 and the A subunit (also called PR65) of this protein phosphatase. In light of the importance of HSF2-PP2A association for HSF2 cellular function, in this study, we have sought to dissect the sequences within HSF2 that are important for interaction with the A subunit of PP2A. The results of these experiments indicate that the HSF2 region comprising amino acids 343-363 is important for A subunit interaction. This region includes part of the C-terminal leucine zipper motif of HSF2 called heptad repeat C (HR-C). The results of transfection/immunoprecipitation experiments also show that deletion of the 6 amino acids from 343 to 348 from HSF2 (HSF2 (delta343-348)), is sufficient to prevent HSF2 from interacting with PP2A. These data provide insight into a new functional domain of HSF2, the PP2A A subunit-interacting region.
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PMID:Identification of the PP2A-interacting region of heat shock transcription factor 2. 1768 98