title: The E3 ligase c-Cbl regulates dendritic cell activation.
abstract: The activation of innate and adaptive immunity is always balanced by inhibitory signalling mechanisms to maintain tissue integrity. We have identified the E3 ligase c-Cbl--known for its roles in regulating lymphocyte signalling--as a modulator of dendritic cell activation. In c-Cbl-deficient dendritic cells, Toll-like receptor-induced expression of proinflammatory factors, such as interleukin-12, is increased, correlating with a greater potency of dendritic-cell-based vaccines against established tumours. This proinflammatory phenotype is accompanied by an increase in nuclear factor (NF)-κB activity. In addition, c-Cbl deficiency reduces both p50 and p105 levels, which have been shown to modulate the stimulatory function of NF-κB. Our data indicate that c-Cbl has a crucial, RING-domain-dependent role in regulating dendritic cell maturation, probably by facilitating the regulatory function of p105 and/or p50.
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Shin-Heng
authors.initials: SH
authors.lastname: Chiou
authors.forename: Payam
authors.initials: P
authors.lastname: Shahi
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Wagner
authors.forename: Hongbo
authors.initials: H
authors.lastname: Hu
authors.forename: Natalia
authors.initials: N
authors.lastname: Lapteva
authors.forename: Mamatha
authors.initials: M
authors.lastname: Seethammagari
authors.forename: Shao-Cong
authors.initials: SC
authors.lastname: Sun
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Levitt
authors.forename: David M
authors.initials: DM
authors.lastname: Spencer
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000096:biosynthesis / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D018664:Interleukin-12 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D002868:Chromosomal Proteins, Non-Histone; D052002:NF-kappa B p50 Subunit; D051193:Toll-Like Receptors; D018664:Interleukin-12; D050721:Proto-Oncogene Proteins c-cbl; C493849:Cbl protein, mouse