Zcchc8 is a glycogen synthase kinase-3 substrate that interacts with RNA-binding proteins.
Phosphorylation of c-Myc on threonine 58 (T58) stimulates its degradation by the Fbw7-SCF ubiquitin ligase. We used a phosphorylation-specific antibody raised against the c-Myc T58 region to attempt to identify other proteins regulated by the Fbw7 pathway. We identified two predominant proteins recognized by this antibody. The first is Ebna1 binding protein 2, a nucleolar protein that, in contrast with a previous report, is likely responsible for the nucleolar staining exhibited by this antibody. The second is Zcchc8, a nuclear protein that is highly phosphorylated in cells treated with nocodazole. We show that Zcchc8 is directly phosphorylated by GSK-3 in vitro and that GSK-3 inhibition prevents Zcchc8 phosphorylation in vivo. Moreover, we found that Zcchc8 interacts with proteins involved in RNA processing/degradation. We suggest that Zcchc8 is a GSK-3 substrate with a role in RNA metabolism.
Gustafson
Michael P
MP
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Welcker
Markus
M
Hwang
Harry C
HC
Clurman
Bruce E
BE
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006801:Humans; D008938:Mitosis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010769:Phosphothreonine / Q000378:metabolism; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D013379:Substrate Specificity
D002352:Carrier Proteins; C432687:EBNA1BP2 protein, human; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins; C506699:ZCCHC8 protein, human; D010769:Phosphothreonine; D012313:RNA; D038362:Glycogen Synthase Kinase 3