A 14,500 MW protein is coded by region E3 of group C human adenoviruses

Tollefson, Ann E.; Krajcsi, Péter; Pursley, Michael; Gooding, Linda R.; Wold, William S.M.

doi:10.1016/0042-6822(90)90182-q

Cited by 50 publications

(45 citation statements)

References 30 publications

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“…(48). Rabbit polyclonal anti-peptide antibody to RID␤ has been described previously (74). Fluorochrome-conjugated, affinity-purified secondary antibodies were purchased from Cappel/ICN (Costa Mesa, Calif.).…”

Section: Methodsmentioning

confidence: 99%

“…These ligands are expressed on activated leukocytes and are also shed in functional form; interact with their cognate receptors, TNF receptor 1 (TNFR1) and Fas (also known as CD95 and ApoI), respectively; and induce apoptosis by activation of caspases. The E3 protein named RID (for receptor internalization and degradation), a complex of the RID␣ and RID␤ proteins (formerly known as E3-10.4K and E3-14.5K), is an integral membrane protein localized primarily on the cell surface (34,67,74,75). RID inhibits apoptosis through the Fas pathway (19,65,72) by stimulating the internalization of cell surface Fas into endosomes, which are transported to lysosomes, where Fas is degraded (72).…”

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confidence: 99%

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Inhibition of TRAIL-Induced Apoptosis and Forced Internalization of TRAIL Receptor 1 by Adenovirus Proteins

Tollefson

Tóth

Doronin

et al. 2001

J Virol

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101

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Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis through two receptors, TRAIL-R1 (also known as death receptor 4) and TRAIL-R2 (also known as death receptor 5), that are members of the TNF receptor superfamily of death domain-containing receptors. We show that human adenovirus type 5 encodes three proteins, named RID (previously named E3-10.4K/14.5K), E3-14.7K, and E1B-19K, that independently inhibit TRAIL-induced apoptosis of infected human cells. This conclusion was derived from studies using wild-type adenovirus, adenovirus replication-competent mutants that lack one or more of the RID, E3-14.7K, and E1B-19K genes, and adenovirus E1-minus replication-defective vectors that express all E3 genes, RID plus E3-14.7K only, RID only, or E3-14.7K only. RID inhibits TRAIL-induced apoptosis when cells are sensitized to TRAIL either by adenovirus infection or treatment with cycloheximide. RID induces the internalization of TRAIL-R1 from the cell surface, as shown by flow cytometry and indirect immunofluorescence for TRAIL-R1. TRAIL-R1 was internalized in distinct vesicles which are very likely to be endosomes and lysosomes. TRAIL-R1 is degraded, as indicated by the disappearance of the TRAIL-R1 immunofluorescence signal. Degradation was inhibited by bafilomycin A1, a drug that prevents acidification of vesicles and the sorting of receptors from late endosomes to lysosomes, implying that degradation occurs in lysosomes. RID was also shown previously to internalize and degrade another death domain receptor, Fas, and to prevent apoptosis through Fas and the TNF receptor. RID was shown previously to force the internalization and degradation of the epidermal growth factor receptor. E1B-19K was shown previously to block apoptosis through Fas, and both E1B-19K and E3-14.7K were found to prevent apoptosis through the TNF receptor. These findings suggest that the receptors for TRAIL, Fas ligand, and TNF play a role in limiting virus infections. The ability of adenovirus to inhibit killing through these receptors may prolong acute and persistent infections.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Inhibition of TRAIL-Induced Apoptosis and Forced Internalization of TRAIL Receptor 1 by Adenovirus Proteins

Tollefson

Tóth

Doronin

et al. 2001

J Virol

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101

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“…(b) Results are representative of three independent experiments performed as described in (a). The multiple bands of RIDb were fully consistent with different post-translational modifications of RIDb (Tollefson et al, 1990), including phosphorylation and O-glycosylation . Interestingly, the higher-and lower-molecular-mass species of RIDb were found on the cell surface and intracellularly, respectively.…”

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confidence: 60%

Adenovirus RID complex enhances degradation of internalized tumour necrosis factor receptor 1 without affecting its rate of endocytosis

Chin

Horwitz

2006

Journal of General Virology

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The receptor internalization and degradation (RID) complex of adenovirus plays an important role in modulating the immune response by downregulating the surface levels of tumour necrosis factor receptor 1 (TNFR1), thereby inhibiting NF-kB activation. Total cellular content of TNFR1 is also reduced in the presence of RID, which can be inhibited by treatment with lysosomotropic agents. In this report, surface biotinylation experiments revealed that, although RID and TNFR1 were able to form a complex on the cell surface, the rate of TNFR1 endocytosis was not affected by RID. However, the degradation of internalized TNFR1 was enhanced significantly in the presence of RID. Therefore, these data suggest that RID downregulates TNFR1 levels by altering the fate of internalized TNFR1 that becomes associated with RID at the plasma membrane, probably by promoting its sorting into endosomal/lysosomal degradation compartments.The successful replication and survival of viruses in the host requires evasion of the immune system. Many of the immunomodulatory genes of adenovirus (Ad) are encoded in early region 3 (E3) (Fessler et al., 2004b;Horwitz, 2004). The E3 receptor internalization and degradation (RID) complex, composed of two RIDa and one RIDb subunits, downregulates a specific set of plasma-membrane receptors, including FAS (Shisler et al., 1997;Elsing & Burgert, 1998;Tollefson et al., 1998), tumour necrosis factor (TNF)-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) (Benedict et al., 2001;Tollefson et al., 2001) and epidermal growth factor receptor (EGFR) (Carlin et al., 1989;Tollefson et al., 1991). Together with another E3 protein, E3/6.7K, RID also reduces the surface expression of TRAIL-R2 (Lichtenstein et al., 2004). Whilst both of the RID subunits are critical for the downregulation of FAS and TRAIL receptors, it appears that the RIDa subunit is sufficient to downregulate EGFR under certain experimental conditions (Hoffman et al., 1990). Recently, we demonstrated that RID also downregulates TNFR1, thereby inhibiting TNF-induced NF-kB activation, which mediates the transcription of a large number of genes involved in inflammation and immune responses such as chemokine expression (Fessler et al., 2004a;Delgado-Lopez & Horwitz, 2006).In vivo experiments have shown that RID is an essential component of the Ad E3 cassette, which facilitates transplantation of allogeneic pancreatic cells (Efrat et al., 1995) and decreases autoimmune type 1 diabetes incidence (von Herrath et al., 1997;Efrat et al., 2001;Pierce et al., 2003). To potentially use RID as a therapeutic immunomodulator, it is important to elucidate the molecular mechanism of RIDmediated downregulation of receptors. We recently showed that the tyrosine sorting motifs of RIDb and clathrin play important roles in the downregulation of TNFR1, and that RID-mediated TNFR1 degradation occurs via an endosomal/ lysosomal pathway (Chin & Horwitz, 2005). In this report, we further examined the effect of RID on TNFR1 trafficking. Specifically, we tested the abili...

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“…The five proteins are E3-gp19K (35), E3-14.7K (47,49), RID␣ (formerly E3-10.4K) (44), RID␤ (formerly E3-14.5K) (43), and E3-6.7K (50). The mechanisms of action of these proteins are of interest for the insights they can provide into cellular processes, for the development of drugs that counteract the action of these proteins, and for the potential use of these proteins to treat human disease.…”

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confidence: 99%

“…RID␣ and RID␤ subunits comprise the RID complex (formerly E3-10.4K/14.5K) (43)(44)(45). RID␤ is a type I integral membrane protein whose signal sequence is cleaved (22) and whose cytoplasmic domain is O glycosylated (24) and phosphorylated on serine 116 (25,28).…”

mentioning

confidence: 99%

Distinct Domains in the Adenovirus E3 RIDα Protein Are Required for Degradation of Fas and the Epidermal Growth Factor Receptor

Zanardi

Yei

Lichtenstein

et al. 2003

J Virol

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A 14,500 MW protein is coded by region E3 of group C human adenoviruses

Cited by 50 publications

References 30 publications

Inhibition of TRAIL-Induced Apoptosis and Forced Internalization of TRAIL Receptor 1 by Adenovirus Proteins

Inhibition of TRAIL-Induced Apoptosis and Forced Internalization of TRAIL Receptor 1 by Adenovirus Proteins

Adenovirus RID complex enhances degradation of internalized tumour necrosis factor receptor 1 without affecting its rate of endocytosis

Distinct Domains in the Adenovirus E3 RIDα Protein Are Required for Degradation of Fas and the Epidermal Growth Factor Receptor

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