Requiem protein links RelB/p52 and the Brm-type SWI/SNF complex in a noncanonical NF-kappaB pathway.
The SWI/SNF chromatin remodeling complex plays pivotal roles in mammalian transcriptional regulation. In this study, we identify the human requiem protein (REQ/DPF2) as an adaptor molecule that links the NF-kappaB and SWI/SNF chromatin remodeling factor. Through in vitro binding experiments, REQ was found to bind to several SWI/SNF complex subunits and also to the p52 NF-kappaB subunit through its nuclear localization signal containing the N-terminal region. REQ, together with Brm, a catalytic subunit of the SWI/SNF complex, enhances the NF-kappaB-dependent transcriptional activation that principally involves the RelB/p52 dimer. Both REQ and Brm were further found to be required for the induction of the endogenous BLC (CXCL13) gene in response to lymphotoxin stimulation, an inducer of the noncanonical NF-kappaB pathway. Upon lymphotoxin treatment, REQ and Brm form a larger complex with RelB/p52 and are recruited to the BLC promoter in a ligand-dependent manner. Moreover, a REQ knockdown efficiently suppresses anchorage-independent growth in several cell lines in which the noncanonical NF-kappaB pathway was constitutively activated. From these results, we conclude that REQ functions as an efficient adaptor protein between the SWI/SNF complex and RelB/p52 and plays important roles in noncanonical NF-kappaB transcriptional activation and its associated oncogenic activity.
Tando
Toshio
T
Division of Host-Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Ishizaka
Aya
A
Watanabe
Hirotaka
H
Ito
Taiji
T
Iida
Shun
S
Haraguchi
Takeshi
T
Mizutani
Taketoshi
T
Izumi
Tomonori
T
Isobe
Toshiaki
T
Akiyama
Taishin
T
Inoue
Jun-ichiro
J
Iba
Hideo
H
D002460:Cell Line; D054382:Chemokine CXCL13 / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D021122:Protein Subunits / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051841:Transcription Factor RelB / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics
C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C113581:DPF2 protein, human; D008233:Lymphotoxin-alpha; D009687:Nuclear Proteins; D021122:Protein Subunits; C084011:SMARCA2 protein, human; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; D051841:Transcription Factor RelB; C084108:SMARCA4 protein, human; D004265:DNA Helicases
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