title: Transducin β-like protein 1 recruits nuclear factor κB to the target gene promoter for transcriptional activation.
abstract: Nuclear factor κB (NF-κB) signaling controls a wide range of cellular functions such as tumor progression and invasion by inducing gene expression. Upon stimulation, NF-κB is translocated to the nucleus and binds to its target gene promoters to activate transcription by recruiting transcription coactivators. Although significant progress has been made in understanding NF-κB-mediated transactivation, little is known about how NF-κB is recruited to its target gene promoters. Here, we report that transducin β-like protein 1 (TBL1) controls the expression of NF-κB target genes by directly binding with NF-κB and facilitating its recruitment to target gene promoters. Tumor necrosis factor alpha stimulation triggered the formation of an NF-κB and TBL1 complex and subsequent target gene promoter binding. Knockdown of TBL1 impaired the recruitment of NF-κB to its target gene promoters. Interestingly, analysis of the Oncomine database revealed that TBL1 mRNA levels were significantly higher in invasive breast cancer tissues than in breast adenocarcinoma tissue. Consistently, TBL1 knockdown significantly reduced the invasive potential of breast cancer cells by inhibiting NF-κB. Our results reveal a new mechanism for the regulation of NF-κB activation, with important implications for the development of novel strategies for cancer therapy by targeting NF-κB.
authors.affiliation: Laboratory of Molecular Signaling, Oral Biology and Medicine, University of California at Los Angeles, Los Angeles, CA 90095-1668, USA.
authors.forename: Sivakumar
authors.initials: S
authors.lastname: Ramadoss
authors.forename: Jiong
authors.initials: J
authors.lastname: Li
authors.forename: Xiangming
authors.initials: X
authors.lastname: Ding
authors.forename: Khalid
authors.initials: K
authors.lastname: Al Hezaimi
authors.forename: Cun-Yu
authors.initials: CY
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D015293:Transducin / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016328:NF-kappa B; C119542:TBL1X protein, human; D014409:Tumor Necrosis Factor-alpha; D015293:Transducin