Small GTPases最新文献_第9页

Rho guanosine nucleotide exchange factors are not such bad guys after all in cancer^a. 鸟苷核苷酸交换因子在癌症中并不是那么坏的家伙。

Small GTPases Pub Date : 2020-07-01 Epub Date: 2018-01-24 DOI: 10.1080/21541248.2018.1423851

Javier Robles-Valero, L Francisco Lorenzo-Martín, Isabel Fernández-Pisonero, Xosé R Bustelo

{"title":"Rho guanosine nucleotide exchange factors are not such bad guys after all in cancera.","authors":"Javier Robles-Valero, L Francisco Lorenzo-Martín, Isabel Fernández-Pisonero, Xosé R Bustelo","doi":"10.1080/21541248.2018.1423851","DOIUrl":"10.1080/21541248.2018.1423851","url":null,"abstract":"Rho GDP/GTP exchange factors (GEFs), the enzymes that trigger the stimulation of Rho GTPases during cell signaling, are widely deemed as potential therapeutic targets owing to their protumorigenic functions. However, the sparse use of animal models has precluded a full understanding of their pathophysiological roles at the organismal level. In a recent article in Cancer Cell, we have reported that the Vav1 GEF unexpectedly acts as a tumor suppressor by mediating the noncatalytic nucleation of cytoplasmic complexes between the E3 ubiquitin ligase Cbl-b and the active Notch1 intracellular domain (ICN1). These complexes favor the ubiquitinylation-mediated degradation of ICN1 in the proteosome and, therefore, the dampening of ICN1 signals in cells. The elimination of Vav1 in mice exacerbates ICN1 signaling in specific thymocyte subpopulations and, in collaboration with ancillary mutations, prompts the development of ICN1-driven T cell acute lymphoblastic leukemia (T-ALL). This new Vav1-dependent pathway antagonizes the fitness of T-ALL of the TLX+ clinical subtype in humans. As a result, VAV1 is found recurrently silenced in both TLX+ T-ALL cell lines and patients. These results call for an overall reevaluation of Rho GEF function in cancer.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":" ","pages":"233-239"},"PeriodicalIF":0.0,"publicationDate":"2020-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549630/pdf/KSGT_11_1423851.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35719863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fast-cycling Rho GTPases. 快速循环的GTPases。

Small GTPases Pub Date : 2020-07-01 Epub Date: 2018-01-29 DOI: 10.1080/21541248.2017.1391365

Pontus Aspenström

引用次数: 33

Reciprocal regulation of YAP/TAZ by the Hippo pathway and the Small GTPase pathway. Hippo通路和Small GTPase通路对YAP/TAZ的相互调控。

Small GTPases Pub Date : 2020-07-01 Epub Date: 2018-04-20 DOI: 10.1080/21541248.2018.1435986

Ju-Won Jang, Min-Kyu Kim, Suk-Chul Bae

{"title":"Reciprocal regulation of YAP/TAZ by the Hippo pathway and the Small GTPase pathway.","authors":"Ju-Won Jang, Min-Kyu Kim, Suk-Chul Bae","doi":"10.1080/21541248.2018.1435986","DOIUrl":"https://doi.org/10.1080/21541248.2018.1435986","url":null,"abstract":"Yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) (YAP/TAZ) are transcriptional coactivators that regulate genes involved in proliferation and transformation by interacting with DNA-binding transcription factors. Remarkably, YAP/TAZ are essential for cancer initiation or growth of most solid tumors. Their activation induces cancer stem cell attributes, proliferation, and metastasis. The oncogenic activity of YAP/TAZ is inhibited by the Hippo cascade, an evolutionarily conserved pathway that is governed by two kinases, mammalian Ste20-like kinases 1/2 (MST1/2) and Large tumor suppressor kinase 1/2 (LATS1/2), corresponding to Drosophila's Hippo (Hpo) and Warts (Wts), respectively. One of the most influential aspects of YAP/TAZ biology is that these factors are transducers of cell structural features, including polarity, shape, and cytoskeletal organization. In turn, these features are intimately related to the cell's ability to attach to other cells and to the surrounding extracellular matrix (ECM), and are also influenced by the cell's microenvironment. Thus, YAP/TAZ respond to changes that occur at the level of whole tissues. Notably, small GTPases act as master organizers of the actin cytoskeleton. Recent studies provided convincing genetic evidence that small GTPase signaling pathways activate YAP/TAZ, while the Hippo pathway inhibits them. Biochemical studies showed that small GTPases facilitate the YAP-Tea domain transcription factor (TEAD) interaction by inhibiting YAP phosphorylation in response to serum stimulation, while the Hippo pathway facilitates the YAP-RUNX3 interaction by increasing YAP phosphorylation. Therefore, small GTPase pathways activate YAP/TAZ by switching its DNA-binding transcription factors. In this review, we summarize the relationship between the Hippo pathway and small GTPase pathways in the regulation of YAP/TAZ.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":" ","pages":"280-288"},"PeriodicalIF":0.0,"publicationDate":"2020-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541248.2018.1435986","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35842770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 28

Shedding new light on RhoA signalling as a drug target in vivo using a novel RhoA-FRET biosensor mouse. 利用新型RhoA- fret生物传感器小鼠，揭示RhoA信号作为体内药物靶点的新进展。

Small GTPases Pub Date : 2020-07-01 Epub Date: 2018-03-21 DOI: 10.1080/21541248.2018.1438024

Max Nobis, David Herrmann, Sean C Warren, Douglas Strathdee, Thomas R Cox, Kurt I Anderson, Paul Timpson

{"title":"Shedding new light on RhoA signalling as a drug target in vivo using a novel RhoA-FRET biosensor mouse.","authors":"Max Nobis, David Herrmann, Sean C Warren, Douglas Strathdee, Thomas R Cox, Kurt I Anderson, Paul Timpson","doi":"10.1080/21541248.2018.1438024","DOIUrl":"10.1080/21541248.2018.1438024","url":null,"abstract":"The small GTPase RhoA is a master regulator of signalling in cell-extracellular matrix interactions. RhoA signalling is critical to many cellular processes including migration, mechanotransduction, and is often disrupted in carcinogenesis. Investigating RhoA activity in a native tissue environment is challenging using conventional biochemical methods; we therefore developed a RhoA-FRET biosensor mouse, employing the adaptable nature of intravital imaging to a variety of settings. Mechanotransduction was explored in the context of osteocyte processes embedded in the calvaria responding in a directional manner to compression stress. Further, the migration of neutrophils was examined during in vivo \"chemotaxis\" in wound response. RhoA activity was tightly regulated during tissue remodelling in mammary gestation, as well as during mammary and pancreatic carcinogenesis. Finally, pharmacological inhibition of RhoA was temporally resolved by the use of optical imaging windows in fully developed pancreatic and mammary tumours in vivo. The RhoA-FRET mouse therefore constitutes a powerful tool to facilitate development of new inhibitors targeting the RhoA signalling axis.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":"11 4","pages":"240-247"},"PeriodicalIF":0.0,"publicationDate":"2020-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549666/pdf/KSGT_11_1438024.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10289600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Light directed migration of a cluster of cells in the centimeter scale. 光引导细胞簇在厘米尺度上的迁移。

Small GTPases Pub Date : 2020-07-01 Epub Date: 2018-01-07 DOI: 10.1080/21541248.2017.1396390

Abdullah Al Mosabbir, Kevin Truong

引用次数: 0

Small change, big effect: Taking RAS by the tail through suppression of post-prenylation carboxylmethylation. 小变化，大作用:通过抑制后戊烯酰化羧甲基化，从尾部服用RAS。

Small GTPases Pub Date : 2020-07-01 Epub Date: 2018-01-25 DOI: 10.1080/21541248.2017.1415637

Hiu Yeung Lau, Mei Wang

{"title":"Small change, big effect: Taking RAS by the tail through suppression of post-prenylation carboxylmethylation.","authors":"Hiu Yeung Lau, Mei Wang","doi":"10.1080/21541248.2017.1415637","DOIUrl":"https://doi.org/10.1080/21541248.2017.1415637","url":null,"abstract":"Mutant RAS isoforms are the most common oncogenes affecting human cancers. After decades of effort in developing drugs targeting oncogenic RAS-driven cancers, we are still charting an unclear path. Despite recent developments exemplified by KRAS (G12C) inhibitors, direct targeting of mutant RAS remains a difficult endeavor. Inhibiting RAS function by targeting its post-translational prenylation processing has remained an important approach, especially with recent progress on the study of isoprenylcysteine carboxylmethyltransferase (ICMT), the unique enzyme for the last step of prenylation processing of RAS isoforms and other substrates. Inhibition of ICMT has shown efficacy both in vitro and in vivo in RAS-mutant cancer models. We will discuss the roles of RAS family of proteins in human cancers and the impact of post-prenylation carboxylmethylation on RAS driven tumorigenesis. In addition, we will review what is known of the molecular and cellular impact of ICMT inhibition on cancer cells that underlie its anti-proliferative and pro-apoptosis efficacy.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":" ","pages":"271-279"},"PeriodicalIF":0.0,"publicationDate":"2020-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541248.2017.1415637","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35673978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Genetic deletion of the Rho GEF Net1 impairs mouse macrophage motility and actin cytoskeletal organization. Rho GEF Net1基因缺失会损害小鼠巨噬细胞运动和肌动蛋白细胞骨架组织。

Small GTPases Pub Date : 2020-07-01 Epub Date: 2017-12-31 DOI: 10.1080/21541248.2017.1405772

Yan Zuo, John d'Aigle, Anjali Chauhan, Jeffrey A Frost

{"title":"Genetic deletion of the Rho GEF Net1 impairs mouse macrophage motility and actin cytoskeletal organization.","authors":"Yan Zuo, John d'Aigle, Anjali Chauhan, Jeffrey A Frost","doi":"10.1080/21541248.2017.1405772","DOIUrl":"https://doi.org/10.1080/21541248.2017.1405772","url":null,"abstract":"Macrophages are innate immune cells that constantly patrol an organism to fulfill protective and homeostatic roles. Previous studies have shown that Rho GTPase activity is required for macrophage mobility, yet the roles of upstream regulatory proteins controlling Rho GTPase function in these cells are not well defined. Previously we have shown that the RhoA GEF Net1 is required for human breast cancer cell motility and extracellular matrix invasion. To assess the role of Net1 in macrophage motility, we isolated bone marrow macrophage (BMM) precursors from wild type and Net1 knockout mice. Loss of Net1 did not affect the ability of BMM precursors to differentiate into mature macrophages in vitro, as measured by CD68 and F4/80 staining. However, Net1 deletion significantly reduced RhoA activation, F-actin accumulation, adhesion, and motility in these cells. Nevertheless, similar to RhoA/RhoB double knockout macrophages, Net1 deletion did not impair macrophage recruitment to the peritoneum in a mouse model of sterile inflammation. These data demonstrate that Net1 is an important regulator of RhoA signaling and motility in mouse macrophages in vitro, but that its function may be dispensable for macrophage recruitment to inflammatory sites in vivo.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":" ","pages":"293-300"},"PeriodicalIF":0.0,"publicationDate":"2020-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541248.2017.1405772","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35583201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Cortactin function in invadopodia. 内胚层的Cortactin功能。

Small GTPases Pub Date : 2020-07-01 Epub Date: 2017-12-31 DOI: 10.1080/21541248.2017.1405773

Pauline Jeannot, Arnaud Besson

引用次数: 36

Expression of a T39N mutant Rab32 protein arrests mitochondria movement within neurites of differentiated SH-SY5Y cells. T39N突变体Rab32蛋白的表达阻止分化SH-SY5Y细胞神经突内线粒体的运动。

Small GTPases Pub Date : 2020-07-01 Epub Date: 2018-01-07 DOI: 10.1080/21541248.2017.1411312

Jonas Rybnicek, Samira Samtleben, Maria Sol Herrera-Cruz, Thomas Simmen

引用次数: 7

Differential requirement of Rab22a for the recruitment of ER-derived proteins to phagosomes and endosomes in dendritic cells. 树突状细胞吞噬体和核内体募集er源性蛋白所需Rab22a的差异。

Small GTPases Pub Date : 2020-05-01 Epub Date: 2018-01-24 DOI: 10.1080/21541248.2017.1384088

Cristina Croce, Luis S Mayorga, Ignacio Cebrian

引用次数: 12