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  • Title: Interaction of PIMT with transcriptional coactivators CBP, p300, and PBP differential role in transcriptional regulation.
    Author: Misra P, Qi C, Yu S, Shah SH, Cao WQ, Rao MS, Thimmapaya B, Zhu Y, Reddy JK.
    Journal: J Biol Chem; 2002 May 31; 277(22):20011-9. PubMed ID: 11912212.
    Abstract:
    PIMT (PRIP-interacting protein with methyltransferase domain), an RNA-binding protein with a methyltransferase domain capable of binding S-adenosylmethionine, has been shown previously to interact with nuclear receptor coactivator PRIP (peroxisome proliferator-activated receptor (PPAR)-interacting protein) and enhance its coactivator function. We now report that PIMT strongly interacts with transcriptional coactivators, CBP, p300, and PBP but not with SRC-1 and PGC-1alpha under in vitro and in vivo conditions. The PIMT binding sites on CBP and p300 are located in the cysteine-histidine-rich C/H1 and C/H3 domains, and the PIMT binding site on PBP is in the region encompassing amino acids 1101-1560. The N-terminal of PIMT (residues 1-369) containing the RNA binding domain interacts with both C/H1 and C/H3 domains of CBP and p300 and with the C-terminal portion of PBP that encompasses amino acids 1371-1560. The C-terminal of PIMT (residues 611-852), which binds S-adenosyl-l-methionine, interacts respectively with the C/H3 domain of CBP/p300 and with a region encompassing amino acids 1101-1370 of PBP. Immunoprecipitation data showed that PIMT forms a complex in vivo with CBP, p300, PBP, and PRIP. PIMT appeared to be co-localized in the nucleus with CBP, p300, and PBP. PIMT enhanced PBP-mediated transcriptional activity of the PPARgamma, as it did for PRIP, indicating synergism between PIMT and PBP. In contrast, PIMT functioned as a repressor of CBP/p300-mediated transactivation of PPARgamma. Based on these observations, we suggest that PIMT bridges the CBP/p300-anchored coactivator complex with the PBP-anchored coactivator complex but differentially modulates coactivator function such that inhibition of the CBP/p300 effect may be designed to enhance the activity of PBP and PRIP.
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