Genomic Structure and Functional Characterisation of the Promoters of Human and Mouse nogo/rtn4

Oertle, Thomas; Huber, Chantal; Putten, Herman van der; Schwab, Martin E.

doi:10.1016/s0022-2836(02)01179-8

Cited by 101 publications

(105 citation statements)

References 70 publications

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“…Western blotting analysis using BMM lysates demonstrated the expression of Nogo-B (Fig. 1A, 1C), corresponding to the Nogo-B1 (∼42 kDa) and -B2 (∼46 kDa) isoforms as reported (33,34). In brain tissues, expression of Nogo-A isoform was detectable in both mRNA and protein levels.…”

Section: Nogo-b Is Indispensable For Full Activation Of Nucleic Acidsmentioning

confidence: 83%

Endoplasmic Protein Nogo-B (RTN4-B) Interacts with GRAMD4 and Regulates TLR9-Mediated Innate Immune Responses

Kimura

Endo

Inui

et al. 2015

The Journal of Immunology

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TLRs are distributed in their characteristic cellular or subcellular compartments to efficiently recognize specific ligands and to initiate intracellular signaling. Whereas TLRs recognizing pathogen-associated lipids or proteins are localized to the cell surface, nucleic acid–sensing TLRs are expressed in endosomes and lysosomes. Several endoplasmic reticulum (ER)–resident proteins are known to regulate the trafficking of TLRs to the specific cellular compartments, thus playing important roles in the initiation of innate immune responses. In this study, we show that an ER-resident protein, Nogo-B (or RTN4-B), is necessary for immune responses triggered by nucleic acid–sensing TLRs, and that a newly identified Nogo-B–binding protein (glucosyltransferases, Rab-like GTPase activators and myotubularins [GRAM] domain containing 4 [GRAMD4]) negatively regulates the responses. Production of inflammatory cytokines in vitro by macrophages stimulated with CpG-B oligonucleotides or polyinosinic:polycytidylic acid was attenuated in the absence of Nogo-B, which was also confirmed in serum samples from Nogo-deficient mice injected with polyinosinic:polycytidylic acid. Although a deficiency of Nogo-B did not change the incorporation or delivery of CpG to endosomes, the localization of TLR9 to endolysosomes was found to be impaired. We identified GRAMD4 as a downmodulator for TLR9 response with a Nogo-B binding ability in ER, because our knockdown and overexpression experiments indicated that GRAMD4 suppresses the TLR9 response and knockdown of Gramd4 strongly enhanced the response in the absence of Nogo-B. Our findings indicate a critical role of Nogo-B and GRAMD4 in trafficking of TLR9.

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Section: Nogo-b Is Indispensable For Full Activation Of Nucleic Acidsmentioning

confidence: 83%

Endoplasmic Protein Nogo-B (RTN4-B) Interacts with GRAMD4 and Regulates TLR9-Mediated Innate Immune Responses

Kimura

Endo

Inui

et al. 2015

The Journal of Immunology

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“…The mammalian reticulon family of proteins consists of four members (RTN1, RTN2, RTN3 and RTN4); the specific functions of most of them are presently poorly understood, although RTN4 (also called Nogo) has been shown to be an inhibitor of axonal extension and neurite outgrowth (Gonzenbach and Schwab 2008). RTN genes are expressed as multiple N-terminal isoforms that are generated by the use of different promoters or by alternative splicing events (Oertle et al, 2003). The C-terminal reticulon domain is evolutionary conserved, whereas the specificity of the N-terminal region contributes to their interaction with a vast array of proteins, such as Bcl-XL and Bcl-2 to reduce their anti-apoptotic activity (Tagami et al, 2000), AP50 and SNARE proteins to regulate endocytosis and exocytosis (Iwahashi and Hamada, 2003;Steiner et al, 2004) or BACE1 to decrease the production of b-amyloid (He et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Acetylation of RTN-1C regulates the induction of ER stress by the inhibition of HDAC activity in neuroectodermal tumors

et al. 2009

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Reticulons are a family of highly conserved proteins, localized in the endoplasmic reticulum (ER) and involved in different cellular functions, such as intracellular membrane trafficking, apoptosis and nuclear envelope formation. The reticulon protein family consists of four members, but their specific functions are presently poorly understood. RTN-1C overexpression triggers apoptosis, regulating ER stress versus DNA damage-induced cell death in a mutually exclusive way. The different RTN isoforms share a C-terminal reticulon homology domain containing two hydrophobic segments and a 66-amino acid hydrophilic loop. In the C-terminal region of RTN-1C, a unique consensus sequence (GAKRH) has recently been identified, showing 100% identity with the DNA-binding domain of histone H4. In this study, we show that this sequence is essential for RTN-1C-mediated apoptosis. It is noteworthy that the lysine 204 present in this region is post-translationally modified by acetylation and that this event is associated with a significant decrease in histone deacetylase activity and contributes to RTN-1C binding to DNA. These data demonstrate a molecular mechanism by which RTN-1C controls apoptosis and indicate this protein to be a novel potential target for cancer therapy.

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“…RTN4 gene, containing eight introns and nine exons and locating on chromosome 2p12-14, can encode three proteins by different splicing, named Nogo-A, Nogo-B and Nogo-C (Oertle et al, 2003). In recent years, more and more attentions have been drawn to the functions of RNT4 gene.…”

Section: Discussionmentioning

confidence: 99%

“…RTN4 gene produced three Nogo isoforms A, B and C through differential splicing and varied promoter usage (Oertle et al, 2003). Nogo-A is mainly expressed in the central nervous system; Nogo-B is expressed in various tissues, such as endothelial cells and smooth muscle cells (Acevedo et al, 2004); Nogo-C is highly expressed in the central nervous system, as well as in skeletal muscle (GrandPre et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

RTN4 3'-UTR Insertion/Deletion Polymorphism and Susceptibility to Non-Small Cell Lung Cancer in Chinese Han Population

Mao²,

Zhou³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Nogo protein, encoded by gene reticulon-4 (RTN4), includes three major isoforms by different splicing, named Nogo-A Nogo-B and Nogo-C. Nogo proteins play an important role in the apoptosis of cells, especially in tumor cells. RTN4 single nucleotide polymorphisms (SNPs) can influence the efficiency of transcription and translation thus being related with an individual's predisposition to cancer. The CAA insertion/deletion polymorphism (rs34917480) within RTN4 3'-UTR has been reported to be associated with many cancer types. In order to investigate the relationship between this polymorphism and susceptibility to non-small cell lung cancer (NSCLC) in the Chinese population, we conducted the present case-control study including 411 NSCLC patients and 471 unrelated healthy controls. The genotype distributions were significantly different between cases and controls (p=0.014). We found that the del allele could significantly increase NSCLC risk (ins/ins vs ins/del: p=0.007, OR 1.46, 95%CI=1.11-1.93; dominant model: p=0.004, OR 1.47, 95%CI=1.13-1.92 and allele model: p=0.008, OR 1.35, 95%CI=1.08-1.67). This association was stronger in participants over 60 years old, males and smokers. We therefore conclude that the CAA insertion/deletion polymorphism (rs34917480) contributes to non-small cell lung cancer risk in Chinese population. Age, sex and environmental exposure are also related to carcinogenic effects of rs34917480 Keywords: RTN4 -polymorphism -rs34917480 -non-small cell lung cancer -susceptibility.

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Genomic Structure and Functional Characterisation of the Promoters of Human and Mouse nogo/rtn4

Cited by 101 publications

References 70 publications

Endoplasmic Protein Nogo-B (RTN4-B) Interacts with GRAMD4 and Regulates TLR9-Mediated Innate Immune Responses

Endoplasmic Protein Nogo-B (RTN4-B) Interacts with GRAMD4 and Regulates TLR9-Mediated Innate Immune Responses

Acetylation of RTN-1C regulates the induction of ER stress by the inhibition of HDAC activity in neuroectodermal tumors

RTN4 3'-UTR Insertion/Deletion Polymorphism and Susceptibility to Non-Small Cell Lung Cancer in Chinese Han Population

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