SINK is a p65-interacting negative regulator of NF-kappaB-dependent transcription.
The transcription factor NF-kappaB plays important roles in inflammation and cell survival. In this study, we identified SINK, an NF-kappaB-inducible protein. Overexpression of SINK inhibited NF-kappaB-dependent transcription induced by tumor necrosis factor (TNF) stimulation or its downstream signaling proteins but did not inhibit NF-kappaB translocation to the nucleus and binding to DNA. Co-immunoprecipitation and in vitro kinase assays indicated that SINK specifically interacted with the NF-kappaB transactivator p65 and inhibited p65 phosphorylation by the catalytic subunit of protein kinase A, which has previously been shown to regulate NF-kappaB activation. Consistent with its role in inhibition of NF-kappaB-dependent transcription, SINK also sensitized cells to apoptosis induced by TNF and TRAIL (TNF-related apoptosis-inducing ligand). Taken together, these data suggest that SINK is critically involved in a novel negative feedback control pathway of NF-kappaB-induced gene expression.
Wu
Min
M
Department of Cell Biology and Genetics, College of Life Sciences, Peking University, Beijing 100871, China.
Xu
Liang-Guo
LG
Zhai
Zhonghe
Z
Shu
Hong-Bing
HB
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D017209:Apoptosis; D018797:Cell Cycle Proteins; D002460:Cell Line; D003001:Cloning, Molecular; D005246:Feedback; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D051996:Transcription Factor RelA; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
D018797:Cell Cycle Proteins; D016328:NF-kappa B; D012097:Repressor Proteins; C474831:TRIB3 protein, human; D051996:Transcription Factor RelA; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases