Far upstream element-binding protein-1, a novel caspase substrate, acts as a cross-talker between apoptosis and the c-myc oncogene.
Far upstream element-binding protein-1 (FBP-1) binds to an upstream element of the c-myc promoter and regulates the c-myc mRNA level. Earlier, FBP-1 was identified as a candidate substrate of caspase-7. Here, we report that FBP-1 is cleaved by executor caspases, both in vitro and during apoptosis. Cleavage occurs at the caspase consensus site (DQPD(74)) located within the classical bipartite nuclear localization signal sequence. In cells subjected to apoptotic stimuli, the caspase-mediated cleavage of FBP-1 leads to its decreased presence in the nucleus, concomitant with the marked downregulation of c-Myc and its various target proteins. By contrast, cells transfected with a non-cleavable mutant of FBP-1 (D74A) maintain higher levels of c-Myc and are protected from apoptosis. On the basis of these results, we suggest that the oncogenic potential of c-Myc is 'switched off' after apoptosis induction as a consequence of the caspase-mediated cleavage of FBP-1.
Jang
M
M
Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
Park
B C
BC
Kang
S
S
Chi
S-W
SW
Cho
S
S
Chung
S J
SJ
Lee
S C
SC
Bae
K-H
KH
Park
S G
SG
D017209:Apoptosis; D001943:Breast Neoplasms / Q000473:pathology; D020169:Caspases / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004265:DNA Helicases / Q000032:analysis / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000502:physiology*; D005260:Female; D016259:Genes, myc; D006801:Humans; D016601:RNA-Binding Proteins
D004268:DNA-Binding Proteins; C492258:FUBP1 protein, human; D016601:RNA-Binding Proteins; D020169:Caspases; D004265:DNA Helicases