The acute myeloid leukemia-associated protein, DEK, forms a splicing-dependent interaction with exon-product complexes.
DEK is an approximately 45-kD phosphoprotein that is fused to the nucleoporin CAN as a result of a (6;9) chromosomal translocation in a subset of acute myeloid leukemias (AMLs). It has also been identified as an autoimmune antigen in juvenile rheumatoid arthritis and other rheumatic diseases. Despite the association of DEK with several human diseases, its function is not known. In this study, we demonstrate that DEK, together with SR proteins, associates with the SRm160 splicing coactivator in vitro. DEK is recruited to splicing factor-containing nuclear speckles upon concentration of SRm160 in these structures, indicating that DEK and SRm160 associate in vivo. We further demonstrate that DEK associates with splicing complexes through interactions mediated by SR proteins. Significantly, DEK remains bound to the exon-product RNA after splicing, and this association requires the prior formation of a spliceosome. Thus, DEK is a candidate factor for controlling postsplicing steps in gene expression that are influenced by the prior removal of an intron from pre-mRNA.
McGarvey
T
T
Banting and Best Department of Medical Research, C.H. Best Institute, University of Toronto, Toronto, Ontario, Canada M5G 1L6.
Rosonina
E
E
McCracken
S
S
Li
Q
Q
Arnaout
R
R
Mientjes
E
E
Nickerson
J A
JA
Awrey
D
D
Greenblatt
J
J
Grosveld
G
G
Blencowe
B J
BJ
D034961:Antigens, Nuclear; D002868:Chromosomal Proteins, Non-Histone; D005091:Exons / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000503:physiopathology; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D012313:RNA / Q000378:metabolism; D012326:RNA Splicing / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000378:metabolism*
D034961:Antigens, Nuclear; D002868:Chromosomal Proteins, Non-Histone; C084738:DEK protein, human; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D016601:RNA-Binding Proteins; C111710:SRRM1 protein, human; D012313:RNA