Ubiquilin Networking in Cancers

Jantrapirom, Salinee; Piccolo, Luca Lo; Pruksakorn, Dumnoensun; Nimlamool, Wutigri

doi:10.3390/cancers12061586

Cited by 14 publications

(12 citation statements)

References 109 publications

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“…In order to investigate the causes of MAD2L2-induced cell apoptosis, the present study focused on the UPP, which is responsible for the majority of intracellular protein degradation ( 29 ). This system exerts its biological effect via the cooperation of E1/E2/E3.…”

Section: Discussionmentioning

confidence: 99%

Oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells

Zhao

et al. 2021

Mol Med Rep

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The clinical efficacy of colorectal tumor treatment is restricted due to platinum agent resistance. Translesion DNA synthesis (TLS) has been shown to contribute to this resistance; however, the exact molecular mechanism remains unknown. The present study aimed to investigate the possible function of the core of the TLS polymerase mitotic arrest deficient 2 like 2 (MAD2L2) in drug sensitivity, in order to provide a treatment rationale for platinum-based chemotherapy in colon cancer. In the present study, MAD2L2 was knocked down using MAD2L2-specific small interfering (si)RNA. HCT116 and SW620 cells were treated with oxaliplatin and MG132; oxaliplatin is a platinum compound that induces DNA damage and MG132 is a potent proteasome inhibitor. Cell viability was determined using an MTT assay. Cell apoptosis was examined via flow cytometry and TUNEL assay. The activity of proteasome 26S subunit, non-ATPase 13 (PSMD13) was detected using ELISA, while the expression levels of apoptotic-related proteins were detected via western blotting. The results demonstrated that cells treated with oxaliplatin or MG132 alone had decreased viability, but a synergistic effect was not observed after co-treatment. In addition, the knockdown of MAD2L2 caused by siMAD2L2 or oxaliplatin treatment increased the expression levels of the pro-apoptotic proteins Bax and Bak and decreased the expression levels of the anti-apoptotic protein Bcl-2, compared with the negative control group. Moreover, MG132 alleviated the decrease in MAD2L2 expression, while reducing siMAD2L2-induced cell apoptosis. These results indicate that oxaliplatin promotes siMAD2L2-induced apoptosis in colon cancer cells. This process was associated with the Bcl-2 and ubiquitin-proteasome pathway. Overall, the present study provides a theoretical basis for improving the clinical efficacy of colon cancer by combining chemotherapy and gene therapy.

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Section: Discussionmentioning

confidence: 99%

Oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells

Zhao

et al. 2021

Mol Med Rep

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“…The Ir7 protein, which interacts with NS4A, is an ortholog of ubiquilin-1. Ubiquilins play important roles in both cytosolic and transmembrane protein degradation pathways, not only as adaptor molecules that shuttle polyubiquitinated proteins to the proteosome, but also as regulators of autophagy and endoplasmic reticulum-associated protein degradation (for a review see [ 78 ]). Proteins of several viruses have been found to interact with ubiquilin family members, as is notably the case for the NS5B protein of hepatitis C virus, whose interaction with human ubiquilin-1 diminishes the half-life of NS5B and which may regulate viral replication [ 79 ], and for the NS4A protein of West Nile virus [ 80 ].…”

Section: Discussionmentioning

confidence: 99%

Exploration of binary protein–protein interactions between tick-borne flaviviruses and Ixodes ricinus

et al. 2021

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Background Louping ill virus (LIV) and tick-borne encephalitis virus (TBEV) are tick-borne flaviviruses that are both transmitted by the major European tick, Ixodes ricinus. Despite the importance of I. ricinus as an arthropod vector, its capacity to acquire and subsequently transmit viruses, known as vector competence, is poorly understood. At the molecular scale, vector competence is governed in part by binary interactions established between viral and cellular proteins within infected tick cells. Methods To investigate virus-vector protein–protein interactions (PPIs), the entire set of open reading frames for LIV and TBEV was screened against an I. ricinus cDNA library established from three embryonic tick cell lines using yeast two-hybrid methodology (Y2H). PPIs revealed for each viral bait were retested in yeast by applying a gap repair (GR) strategy, and notably against the cognate protein of both viruses, to determine whether the PPIs were specific for a single virus or common to both. The interacting tick proteins were identified by automatic BLASTX, and in silico analyses were performed to expose the biological processes targeted by LIV and TBEV. Results For each virus, we identified 24 different PPIs involving six viral proteins and 22 unique tick proteins, with all PPIs being common to both viruses. According to our data, several viral proteins (pM, M, NS2A, NS4A, 2K and NS5) target multiple tick protein modules implicated in critical biological pathways. Of note, the NS5 and pM viral proteins establish PPI with several tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which are essential adaptor proteins at the nexus of multiple signal transduction pathways. Conclusion We provide the first description of the TBEV/LIV-I. ricinus PPI network, and indeed of any PPI network involving a tick-borne virus and its tick vector. While further investigation will be needed to elucidate the role of each tick protein in the replication cycle of tick-borne flaviviruses, our study provides a foundation for understanding the vector competence of I. ricinus at the molecular level. Indeed, certain PPIs may represent molecular determinants of vector competence of I. ricinus for TBEV and LIV, and potentially for other tick-borne flaviviruses.

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“…The Ir7 protein, which interacts with NS4A, is an ortholog of ubiquilin-1. Ubiquilins play important roles in both cytosolic and transmembrane protein degradation pathways, not only as adaptor molecules that shuttle polyubiquitinated proteins to the proteosome, but also as regulators of autophagy and endoplasmic reticulum-associated protein degradation (for a review see [77]). Proteins of several viruses have been found to interact with ubiquilin family members, as is notably the case for the NS5B protein of hepatitis C virus, whose interaction with human ubiquilin-1 diminishes the half-life of NS5B and which may regulate viral replication [78] and for the NS4A protein of West Nile virus [79].…”

Section: Signal Transduction / Transcriptional Response / Protein Degmentioning

confidence: 99%

Exploration of Binary Protein-Protein Interactions Between Tick-Borne Flaviviruses and Ixodes Ricinus

LEMASSON

CAIGNARD

UNTERFINGER

et al. 2020

Preprint

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BackgroundLouping ill virus (LIV) and tick-borne encephalitis virus (TBEV) are tick-borne flaviviruses that are both transmitted by the major European tick, Ixodes ricinus. Despite the importance of I. ricinus as an arthropod vector, its capacity to acquire and subsequently transmit viruses, known as vector competence, is poorly understood. At the molecular scale, vector competence is governed in part by binary interactions established between viral and cellular proteins within infected tick cells.MethodsTo investigate virus-vector protein-protein interactions (PPIs), the entire set of open reading frames for LIV and TBEV was screened against an I. ricinus cDNA library established from three embryonic tick cell lines using yeast two-hybrid methodology (Y2H). PPIs revealed for each viral bait were retested in yeast by applying a gap repair (GR) strategy and notably against the cognate protein of both viruses, to determine whether the PPIs were specific for a single virus or common to both. The interacting tick proteins were identified by automatic BLASTX and in silico analyses were performed to expose the biological processes targeted by LIV and TBEV.ResultsFor each virus, we identified 24 different PPIs involving six viral proteins and 22 unique tick proteins, with all PPIs being common to both viruses. According to our data, several viral proteins (pM, M, NS2A, NS4A, 2K and NS5) target multiple tick protein modules implicated in critical biological pathways. Of note, the NS5 and pM viral proteins establish PPI with several tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which are essential adaptor proteins at the nexus of multiple signal transduction pathways.ConclusionWe provide the first description of the TBEV/LIV-I. ricinus PPI network, and indeed of any PPI network involving a tick-borne virus and its tick vector. While further investigation will be needed to elucidate the role of each tick protein in the replication cycle of tick-borne flaviviruses, our study provides a foundation for understanding the vector competence of I. ricinus at the molecular level. Indeed, certain PPIs may represent molecular determinants of vector competence of I. ricinus for TBEV and LIV, and potentially for other tick-borne flaviviruses.

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Ubiquilin Networking in Cancers

Cited by 14 publications

References 109 publications

Oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells

Oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells

Exploration of binary protein–protein interactions between tick-borne flaviviruses and Ixodes ricinus

Exploration of Binary Protein-Protein Interactions Between Tick-Borne Flaviviruses and Ixodes Ricinus

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