title: The F-box protein Skp2 participates in c-Myc proteosomal degradation and acts as a cofactor for c-Myc-regulated transcription.
abstract: The transcription regulatory oncoprotein c-Myc controls genes involved in cell growth, apoptosis, and oncogenesis. c-Myc is turned over very quickly through the ubiquitin/proteasome pathway. The proteins involved in this process are still unknown. We have found that Skp2 interacts with c-Myc and participates in its ubiquitylation and degradation. The interaction between Skp2 and c-Myc occurs during the G1 to S phase transition of the cell cycle in normal lymphocytes. Surprisingly, Skp2 enhances c-Myc-induced S phase transition and activates c-Myc target genes in a Myc-dependent manner. Further, Myc-induced transcription was shown to be Skp2 dependent, suggesting interdependence between c-Myc and Skp2 in activation of transcription. Moreover, Myc-dependent association of Skp2, ubiquitylated proteins, and subunits of the proteasome to a c-Myc target promoter was demonstrated in vivo. The results suggest that Skp2 is a transcriptional cofactor for c-Myc and indicates a close relationship between transcription activation and transcription factor ubiquitination.
authors.affiliation: Department of Plant Biology and Forest Genetics, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden.
authors.forename: Natalie
authors.initials: N
authors.lastname: von der Lehr
authors.forename: Sara
authors.initials: S
authors.lastname: Johansson
authors.forename: Siqin
authors.initials: S
authors.lastname: Wu
authors.forename: Fuad
authors.initials: F
authors.lastname: Bahram
authors.forename: Alina
authors.initials: A
authors.lastname: Castell
authors.forename: Cihan
authors.initials: C
authors.lastname: Cetinkaya
authors.forename: Per
authors.initials: P
authors.lastname: Hydbring
authors.forename: Ingrid
authors.initials: I
authors.lastname: Weidung
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakayama
authors.forename: Keiichi I
authors.initials: KI
authors.lastname: Nakayama
authors.forename: Ola
authors.initials: O
authors.lastname: Söderberg
authors.forename: Tom K
authors.initials: TK
authors.lastname: Kerppola
authors.forename: Lars-Gunnar
authors.initials: LG
authors.lastname: Larsson
mesh_terms: D000818:Animals; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D056742:Cyclin D2; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005809:Genes, Regulator / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D016196:S Phase / Q000235:genetics; D044786:S-Phase Kinase-Associated Proteins; D015533:Transcriptional Activation / Q000235:genetics; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism
chemical_list: C080336:CCND2 protein, human; D018797:Cell Cycle Proteins; D056742:Cyclin D2; D016213:Cyclins; C489427:MYC protein, human; D009097:Multienzyme Complexes; D016271:Proto-Oncogene Proteins c-myc; D044786:S-Phase Kinase-Associated Proteins; D025801:Ubiquitin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex