Human TNFα-induced protein 3-interacting protein 1 (TNIP1) promoter activation is regulated by retinoic acid receptors

Gurevich, I. B.; Zhang, Carmen; Francis, Nidhish; Struzynsky, Charles P.; Livings, Sarah E.; Aneskievich, Brian J.

doi:10.1016/j.gene.2012.11.041

Cited by 10 publications

(8 citation statements)

References 36 publications

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“…The TNIP1 promoter contains retinoic acid response elements (RARE) and retinoid-acid-receptor binding sites. These elements are involved in the induction of TNIP1 expression by retinoic acid under permissive epigenetic conditions in different cell lines ( 19 ). Since ATRA is an effective drug used for acne treatment, we examined whether this compound is capable of regulating TNIP1 and, thus, the expression of downstream targets of the TLR signaling pathway in keratinocytes.…”

Section: Resultsmentioning

confidence: 99%

“…Earlier studies found functional RARE elements in the TNIP1 promoter region, and that TNIP1 was induced by ATRA in HeLa cells under permissive epigenetic conditions, in the presence of Trichostatin A co-treatment ( 19 ). Trichostatin A inhibits histone deacetylase I and II and alters gene expression by opening chromatin and allowing transcription factors to bind, thus, promoting transcription of different genes.…”

Section: Discussionmentioning

confidence: 96%

“…Retinoids have been shown to promote cell proliferation, inhibit keratinocyte terminal differentiation, decrease the size of sebaceous glands and, indirectly, reduce the amount of C. acnes ( 40 ). Studies of the effect of retinoids on innate immunity are limited, and the results are often dependant on the cells used ( 19 , 41 – 44 ). In most cases, ATRA application to monocytes and macrophages decreased TLR2 abundance as well as the expression of selected pro-inflammatory mediators; however, the mechanism of these effects remains unclear ( 43 , 45 , 46 ).…”

Section: Discussionmentioning

confidence: 99%

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TNIP1 Regulates Cutibacterium acnes-Induced Innate Immune Functions in Epidermal Keratinocytes

et al. 2018

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Human skin cells recognize the presence of the skin microbiome through pathogen recognition receptors. Epidermal keratinocytes are known to activate toll-like receptors (TLRs) 2 and 4 in response to the commensal Cutibacterium acnes (C. acnes, formerly known as Propionibacterium acnes) bacterium and subsequently to induce innate immune and inflammatory events. These events may lead to the appearance of macroscopic inflammatory acne lesions in puberty: comedos, papules and, pustules. Healthy skin does not exhibit inflammation or skin lesions, even in the continuous presence of the same microbes. As the molecular mechanism for this duality is still unclear, we aimed to identify factors and mechanisms that control the innate immune response to C. acnes in keratinocytes using a human immortalized keratinocyte cell line, HPV-KER, normal human keratinocytes (NHEK) and an organotypic skin model (OSM). TNIP1, a negative regulator of the NF-κB signaling pathway, was found to be expressed in HPV-KER cells, and its expression was rapidly induced in response to C. acnes treatment, which was confirmed in NHEK cells and OSMs. Expression changes were not dependent on the C. acnes strain. However, we found that the extent of expression was dependent on C. acnes dose. Bacterial-induced changes in TNIP1 expression were regulated by signaling pathways involving NF-κB, p38, MAPKK and JNK. Experimental modification of TNIP1 levels affected constitutive and C. acnes-induced NF-κB promoter activities and subsequent inflammatory cytokine and chemokine mRNA and protein levels. These results suggest an important role for this negative regulator in the control of bacterially induced TLR signaling pathways in keratinocytes. We showed that all-trans retinoic acid (ATRA) induced elevated TNIP1 expression in HPV-KER cells and also in OSMs, where TNIP1 levels increased throughout the epidermis. ATRA also reduced constitutive and bacterium-induced levels of TNFα, CCL5 and TLR2, while simultaneously increasing CXCL8 and TLR4 expression. Based on these findings, we propose that ATRA may exhibit dual effects in acne therapy by both affecting the expression of the negative regulator TNIP1 and attenuating TLR2-induced inflammation. Overall, TNIP1, as a possible regulator of C. acnes-induced innate immune and inflammatory events in keratinocytes, may play important roles in the maintenance of epidermal homeostasis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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TNIP1 Regulates Cutibacterium acnes-Induced Innate Immune Functions in Epidermal Keratinocytes

et al. 2018

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“…Among these proteins, dystrophin (DMD), which has different isoforms expressed in muscle and in brain, plays a role in synapse structure and function . TNFAIP3‐interacting protein (TNIP1) is a corepressor of agonist‐bound retinoic acid receptors (RARs) and a regulator of nuclear factor κB (NF‐kB) pathway . This protein has been identified in exosomes from patients with neural tube defects .…”

Section: Resultsmentioning

confidence: 99%

Proteomic Analysis of Neuroblastoma‐Derived Exosomes: New Insights into a Metastatic Signature

et al. 2017

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Neuroblastoma (NB) is the most common extracranial pediatric solid tumor. Around 70% of patients with metastatic disease at diagnosis present bone-marrow infiltration, which is considered a marker of poor outcome; however, the mechanism underlying this specific tropism has to be elucidated. Tumor-derived exosomes may support metastatic progression in several tumors by interacting with the microenvironment, and may serve as tumor biomarkers. The main objective of this study is to identify an exosomal signature associated with NB metastatic bone-marrow dissemination. Therefore, the proteomic cargo of exosomes isolated from NB cell lines derived from primary tumor and bone-marrow metastasis is characterized. The comparison among exosomal proteins show 15 proteins exclusively present in primary tumor-derived exosomes, mainly involved in neuronal development, and 6 proteins in metastasis-derived exosomes related to cancer progression. Significant proteins obtain with statistical analysis performed between the two groups, reveal that primary tumor exosomes contain a higher level of proteins involved in extra-cellular matrix (ECM) assembly and adhesion, as well as in neuronal development. Exosomes isolated from bone-marrow metastasis exhibit proteins involved in ameboidal cell migration and mitochondrial activity. This work suggests that proteomic profiling of NB-derived exosomes reflects the tumor stage and may be considered as potential tumor biomarker.

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“…To examine the impact of PRMT3-ALDH1A1 interaction on gene-expression regulation by RA in vivo, we measured the mRNA levels of RA-responsive genes [39][40][41][42][43][44][45] involved in diverse biological processes (Supplementary Table 2) (i) with or without overexpressing wild-type PRMT3 or PRMT3-E338Q mutant, (ii) with control siRNA or PRMT3 specific siRNA and (iii) in the presence or absence of RALD using quantitative RT-PCR (Fig. 6 and Supplementary Fig.…”

Section: A L D H 1 a 2 A L D H 1 Amentioning

confidence: 99%

PRMT3 interacts with ALDH1A1 and regulates gene-expression by inhibiting retinoic acid signaling

et al. 2021

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Protein arginine methyltransferase 3 (PRMT3) regulates protein functions by introducing asymmetric dimethylation marks at the arginine residues in proteins. However, very little is known about the interaction partners of PRMT3 and their functional outcomes. Using yeast-two hybrid screening, we identified Retinal dehydrogenase 1 (ALDH1A1) as a potential interaction partner of PRMT3 and confirmed this interaction using different methods. ALDH1A1 regulates variety of cellular processes by catalyzing the conversion of retinaldehyde to retinoic acid. By molecular docking and site-directed mutagenesis, we identified the specific residues in the catalytic domain of PRMT3 that facilitate interaction with the C-terminal region of ALDH1A1. PRMT3 inhibits the enzymatic activity of ALDH1A1 and negatively regulates the expression of retinoic acid responsive genes in a methyltransferase activity independent manner. Our findings show that in addition to regulating protein functions by introducing methylation modifications, PRMT3 could also regulate global gene expression through protein-protein interactions.

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Human TNFα-induced protein 3-interacting protein 1 (TNIP1) promoter activation is regulated by retinoic acid receptors

Cited by 10 publications

References 36 publications

TNIP1 Regulates Cutibacterium acnes-Induced Innate Immune Functions in Epidermal Keratinocytes

TNIP1 Regulates Cutibacterium acnes-Induced Innate Immune Functions in Epidermal Keratinocytes

Proteomic Analysis of Neuroblastoma‐Derived Exosomes: New Insights into a Metastatic Signature

PRMT3 interacts with ALDH1A1 and regulates gene-expression by inhibiting retinoic acid signaling

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