Mechanisms of HBx Mediated Liver Cancer: Multiple Pathways and Opportunities

Feitelson, Mark A.; Arzumanyan, Alla; Friedman, Tiffany; Şatıroğlu-Tufan, N. Lale; Lian, Zhaorui; Clayton, Marcia M.; Kang, Je-Won; Reis, Helena M. G. P. V.; Pan, Jingbo; Liu, Jie; Arbuthnot, Patrick; Kew, Michael C.

doi:10.5772/27962

Cited by 2 publications

(1 citation statement)

References 155 publications

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“…The URG7 gene (745 base pairs, located on chromosome 16 in position “p13.1”) codes for a polypeptide of 99 amino acids, with the first 74 residues of the sequence overlapping with the N-terminal portion of the MRP6 protein, also known as ABCC6 (it is considered as its isoform 2), a protein belonging to the ABC (ATP-binding cassette) superfamily; the remaining 25 amino acids are peculiar to the URG7 protein [ 5 ]. The expression level of URG7 increases significantly during hepatitis B virus (HBV) infection, by the viral protein HBXAg (hepatitis B virus X antigen) transactivating activity [ 7 , 8 ], and its proven antiapoptotic activity has been related to the mitigation of ER stress, with a reduction in protein misfolding, favoring overall cell survival [ 9 ]. If the antiapoptotic effect of URG7 up-regulation in liver cells infected by hepatitis B virus could be considered deleterious, in neuronal cells the same effect could be protective with respect to neurodegeneration [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effect of Antiapoptotic URG7 Protein on Human Neuroblastoma Cell Line SH-SY5Y

Nigro,

Miglionico,

Carmosino

et al. 2023

IJMS

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Up-regulated Gene clone 7 (URG7) is a protein localized in the endoplasmic reticulum (ER) and overexpressed in liver cells upon hepatitis B virus (HBV) infection. Its activity has been related to the attenuation of ER stress resulting from HBV infection, promoting protein folding and ubiquitination and reducing cell apoptosis overall. While the antiapoptotic activity of URG7 in HBV-infected cells may have negative implications, this effect could be exploited positively in the field of proteinopathies, such as neurodegenerative diseases. In this work, we aimed to verify the possible contribution of URG7 as a reliever of cellular proteostasis alterations in a neuronal in vitro system. Following tunicamycin-induced ER stress, URG7 was shown to modulate different markers of the unfolded protein response (UPR) in favor of cell survival, mitigating ER stress and activating autophagy. Furthermore, URG7 promoted ubiquitination, and determined a reduction in protein aggregation, calcium release from the ER and intracellular ROS content, confirming its pro-survival activity. Therefore, in light of the results reported in this work, we hypothesize that URG7 offers activity as an ER stress reliever in a neuronal in vitro model, and we paved the way for a new approach in the treatment of neurodegenerative diseases.

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