title: SUMOylation regulates the nuclear mobility of CREB binding protein and its association with nuclear bodies in live cells.
abstract: The lysine acetyltransferase CREB binding protein (CBP) is required for chromatin modification and transcription at many gene promoters. In fixed cells, a large proportion of CBP colocalises to PML or nuclear bodies. Using live cell imaging, we show here that YFP-tagged CBP expressed in HEK293 cells undergoes gradual accumulation in nuclear bodies, some of which are mobile and migrate towards the nuclear envelope. Deletion of a short lysine-rich domain that contains the major SUMO acceptor sites of CBP abrogated its ability to be SUMO modified, and prevented its association with endogenous SUMO-1/PML speckles in vivo. This SUMO-defective CBP showed enhanced ability to co-activate AML1-mediated transcription. Deletion mapping revealed that the SUMO-modified region was not sufficient for targeting CBP to PML bodies, as C-terminally truncated mutants containing this domain showed a strong reduction in accumulation at PML bodies. Fluorescence recovery after photo-bleaching (FRAP) experiments revealed that YFP-CBPDelta998-1087 had a retarded recovery time in the nucleus, as compared to YFP-CBP. These results indicate that SUMOylation regulates CBP function by influencing its shuttling between nuclear bodies and chromatin microenvironments.
authors.affiliation: Gene Regulation Group, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom.
authors.forename: Colm M
authors.initials: CM
authors.lastname: Ryan
authors.forename: Karin B
authors.initials: KB
authors.lastname: Kindle
authors.forename: Hilary M
authors.initials: HM
authors.lastname: Collins
authors.forename: David M
authors.initials: DM
authors.lastname: Heery
mesh_terms: D000818:Animals; D019556:COS Cells; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006801:Humans; D025842:SUMO-1 Protein / Q000378:metabolism*; D017384:Sequence Deletion
chemical_list: D025842:SUMO-1 Protein; D050882:CREB-Binding Protein