UXT is a novel and essential cofactor in the NF-kappaB transcriptional enhanceosome.
As a latent transcription factor, nuclear factor kappaB (NF-kappaB) translocates from the cytoplasm into the nucleus upon stimulation and mediates the expression of genes that are important in immunity, inflammation, and development. However, little is known about how it is regulated inside the nucleus. By a two-hybrid approach, we identify a prefoldin-like protein, ubiquitously expressed transcript (UXT), that is expressed predominantly and interacts specifically with NF-kappaB inside the nucleus. RNA interference knockdown of UXT leads to impaired NF-kappaB activity and dramatically attenuates the expression of NF-kappaB-dependent genes. This interference also sensitizes cells to apoptosis by tumor necrosis factor-alpha. Furthermore, UXT forms a dynamic complex with NF-kappaB and is recruited to the NF-kappaB enhanceosome upon stimulation. Interestingly, the UXT protein level correlates with constitutive NF-kappaB activity in human prostate cancer cell lines. The presence of NF-kappaB within the nucleus of stimulated or constitutively active cells is considerably diminished with decreased endogenous UXT levels. Our results reveal that UXT is an integral component of the NF-kappaB enhanceosome and is essential for its nuclear function, which uncovers a new mechanism of NF-kappaB regulation.
Sun
Shaogang
S
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Tang
Yujie
Y
Lou
Xiwen
X
Zhu
Lianhui
L
Yang
Kai
K
Zhang
Bianhong
B
Shi
Hexin
H
Wang
Chen
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D019084:Fluorescent Antibody Technique, Indirect; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D018832:Molecular Chaperones; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins; D011471:Prostatic Neoplasms / Q000473:pathology; D034622:RNA Interference; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020798:Two-Hybrid System Techniques
D018797:Cell Cycle Proteins; D018832:Molecular Chaperones; D016328:NF-kappa B; D009363:Neoplasm Proteins; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C118920:UXT protein, human; D008156:Luciferases