Уважаемые коллеги, доброго времени суток! Представляем вам нидерландское научное издание Cell Biology and Toxicology. Журнал имеет второй квартиль, издается в Springer Netherlands, его SJR за 2021 г. равен 0,8, пятилетний импакт-фактор - 4,877, печатный ISSN - 0742-2091, электронный - 1573-6822, предметные области - Здоровье, токсикологии и мутации, Токсикология, Клеточная биология. Вот так выглядит обложка:
Редактором является Хиангдонг Ванг, контактные данные - keildeinniel.reyes@springernature.com, Michelle.Jolbot@springer.com, journalpermissions@springernature.com, maggie.zhang@springernature.com.
Это международный журнал, посвященный клиническим и трансляционным исследованиям с акцентом на молекулярную и клеточную биологию, генетическую и эпигенетическую гетерогенность, открытие и разработку лекарств, а также молекулярную фармакологию и токсикологию. Он ориентирован на конкретные заболевания, уделяя приоритетное внимание публикациям по регуляции на основе генов и белков, дисфункции внутриклеточных сигнальных путей, функции, зависящей от типа клеток, и системам биомедицины при открытии и разработке лекарств. К публикации принимаются оригинальные статьи с выдающимися, инновационными и значимыми результатами, важные обзоры последних достижений в области исследований и проблем, представляющих большой интерес в настоящее время, статьи с мнениями о передовых научных достижениях, а также оперативные сообщения или отчеты о молекулярных механизмах и методах лечения заболеваний.
Адрес издания - https://www.springer.com/journal/10565/editors
Пример статьи, название - Inhibition of USP14 enhances anti-tumor effect in vemurafenib-resistant melanoma by regulation of Skp2. Заголовок (Abstract)
Background
The mutation of BRAF V600E often occurred in melanoma and results in tumorigenesis. BRAF mutation drives hyperactivation of the RAF-MAPK-ERK pathway. The acquired drug resistance upon prolonged use of BRAF inhibitors (such as vemurafenib) still remains the main obstacle. Previously, we have found that E3 ligase Skp2 over-expresses vemurafenib-resistant melanoma cells, and knockdown of Skp2 enhances the anti-tumor effect of vemurafenib. Interestingly, the literature has reported that the selective USP14/UCHL5 inhibitor b-AP15 displays great potential in melanoma therapy; however, the molecular mechanism still remains unknown.
Methods
In vitro, the effect of the combination regimen of vemurafenib (Vem, PLX4032) and b-AP15 on vem-sensitive and vem-resistant melanoma has been investigated by wound healing, colony formation, transwell invasion assay, flow cytometry, lysosome staining, and ROS detection. In vivo, the combination effect on vem-resistant melanoma has been evaluated with a nude mice xenograft tumor model. GST-pulldown and co-immunoprecipitation (co-IP) assays have been applied to investigate the interactions between USP14, UCHL5, and Skp2. Cycloheximide (CHX) assay and ubiquitination assays have been used to explore the effect of USP14 on Skp2 protein half-life and ubiquitination status.
Results
In the present study, we have revealed that repression of USP14 sensitizes vemurafenib resistance in melanoma through a previously unappreciated mechanism that USP14 but not UCHL5 stabilizes Skp2, blocking its ubiquitination. K119 on Skp2 is required for USP14-mediated deubiquitination and stabilization of Skp2. Furthermore, the mutated catalytic activity amino acid cysteine (C) 114 on USP14 abrogates stabilization of Skp2. Stabilization of Skp2 is required for USP14 to negatively regulate autophagy. The combination regimen of Skp2 inhibitor vemurafenib and USP14/UCHL5 inhibitor b-AP15 dramatically inhibits cell viability, migration, invasion, and colony formation in vemurafenib-sensitive and vemurafenib-resistant melanoma. Vemurafenib and b-AP15 hold cells in the S phase thus leading to apoptosis as well as the formation of the autophagic vacuole in vemurafenib-resistant SKMEL28 cells. The enhanced proliferation effect of USP14 and Skp2 is mainly due to a more effective reduction of cell apoptosis and autophagy. Further evaluation of various protein alterations has revealed that the increased expression of cleaved-PARP, LC3, and decreased Ki67 are more obvious in the combination of vemurafenib and b-AP15 treatment than those in single-drug treatment. Moreover, the co-treatment of vemurafenib and b-AP15 dramatically inhibits the growth of vemurafenib-resistant melanoma xenograft in vivo. Collectively, our findings have demonstrated that the combination of Skp2 inhibitor and USP14 inhibitor provides a new solution for the treatment of BRAF inhibitor resistance melanoma.
Keywords: BRAF V600E; Vemurafenib; Resistance; USP14; Skp2; Autophagy; Melanoma