title: The CCAAT box-binding transcription factor NF-Y regulates basal expression of human proteasome genes.
abstract: Protein degradation by the proteasome plays an important role in all major cellular pathways. Aberrant proteasome activity is associated with numerous human diseases including cancer and neurological disorders, but the underlying mechanism is virtually unclear. At least part of the reason for this is due to lack of understanding of the regulation of human proteasome genes. In this study, we found that a large set of human proteasome genes carry the CCAAT box in their promoters. We further demonstrated that the basal expression of these CCAAT box-containing proteasome genes is regulated by the transcription factor NF-Y. Knockdown of NF-YA, an essential subunit of NF-Y, reduced proteasome gene expression and compromised the cellular proteasome activity. In addition, we showed that knockdown of NF-YA sensitized breast cancer cells to the proteasome inhibitor MG132. This study unveils a new role for NF-Y in the regulation of human proteasome genes and suggests that NF-Y may be a potential target for cancer therapy.
authors.affiliation: Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Haiming
authors.initials: H
authors.lastname: Xu
authors.forename: Jiejun
authors.initials: J
authors.lastname: Fu
authors.forename: Seung-Wook
authors.initials: SW
authors.lastname: Ha
authors.forename: Donghong
authors.initials: D
authors.lastname: Ju
authors.forename: Jianpu
authors.initials: J
authors.lastname: Zheng
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Youming
authors.initials: Y
authors.lastname: Xie
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D002460:Cell Line; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008969:Molecular Sequence Data; D010802:Phylogeny; D011401:Promoter Regions, Genetic / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000235:genetics* / Q000378:metabolism; D061988:Proteasome Inhibitors; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics
chemical_list: D023081:CCAAT-Binding Factor; D007976:Leupeptins; C492061:NFYA protein, human; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde