Rho GTPases at the crossroad of signaling networks in mammals

Hervé, Jean Claude; Bourmeyster, Nicolas

doi:10.1080/21541248.2015.1044811

Cited by 27 publications

(24 citation statements)

References 40 publications

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“…It has been reported that the Rho signaling pathway exerts its effects on cellular activities primarily through its central role in actin cytoskeleton dynamics (27). A reciprocal relationship has also been explored between Rho proteins and microtubules (28,29) and it has been demonstrated that the activation of the Rho pathway altered the activity of microtubule associated protein Figure 6. Analysis of the expression of SIRT5 and clinical outcomes of breast cancer patients (Oncomine database and Kaplan-Meier plotter derived from http://kmplot.com/analysis/).…”

Section: Discussionmentioning

confidence: 99%

SIRT5 as a biomarker for response to anthracycline-taxane-based neoadjuvant chemotherapy in triple-negative breast cancer

Che

Song

et al. 2018

Oncol Rep

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Neoadjuvant chemotherapy (NAC) is of great importance for patients with triple-negative breast cancer (TNBC) and the achievement of pathological complete response (pCR) to NAC in TNBC patients indicates survival benefits. However, the identification of reliable predictive biomarkers of pCR to NAC in TNBC patients remains an urgent and largely unattended medical issue. In the present study, we evaluated the differentially expressed genes (DEGs) between pCR and non-pCR patients after doxorubicin/cyclophosphamide therapy, followed by paclitaxel pre-operative treatment in 64 TNBC patients recorded in the GSE41998 dataset of Gene Expression Omnibus and identified 118 DEGs. Subsequently, we selected five core genes that were closely associated with the pCR of TNBC patients by using a genetic algorithm‑support vector machine-based method. Sirtuin 5 (SIRT5) was one of the five core genes and patients who achieved pCR expressed higher levels of SIRT5. Thus, we speculated that SIRT5 may be a potential predictive marker of the response to anthracycline-taxane-based chemotherapy. Oncomine analysis revealed that the expression levels of SIRT5 were higher in epirubicin/cyclophosphamide-docetaxel responders compared with non-responders. Furthermore, Gene Ontology analysis indicated that SIRT5 may affect the response to anthracycline-taxane-based chemotherapy by regulating the Rho pathway. It was also observed that SIRT5 was upregulated in TNBC and breast cancer with BRCA1 mutation subtypes. High SIRT5 expression was also associated with poor clinical outcomes of breast cancer patients. In conclusion, the present study revealed SIRT5 as a biomarker for response to anthracycline-taxane-based NAC in patients with TNBC and identified a series of novel biological functions of SIRT5 in breast cancer.

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Section: Discussionmentioning

confidence: 99%

SIRT5 as a biomarker for response to anthracycline-taxane-based neoadjuvant chemotherapy in triple-negative breast cancer

Che

Song

et al. 2018

Oncol Rep

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“…In blood vessels, the Rho/Rho-associated protein kinase (ROCK) pathway is expressed abundantly in the vascular smooth muscle and is known to regulate vasoreactivity4445. Noteworthy in this context is that this family of proteins is recognized as key signalling molecules that regulate arterial blood pressure and are important mediators involved in maintaining vascular tone in pathophysiological conditions, such as hypertension4647. Hence, any alterations in the hemodynamic balance and level of activation of the Rho protein family members may compromise the vascular integrity and lead to various vasculopathies4348.…”

Section: Discussionmentioning

confidence: 99%

First insight into the proteome landscape of the porcine short posterior ciliary arteries: Key signalling pathways maintaining physiologic functions

Manicam

Perumal

Pfeiffer

et al. 2016

Sci Rep

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Short posterior ciliary arteries (sPCA) provide the major blood supply to the optic nerve head. Emerging evidence has linked structural and functional anomalies of sPCA to the pathogenesis of several ocular disorders that cause varying degrees of visual loss, particularly anterior ischaemic optic neuropathy and glaucoma. Although the functional relevance of this vascular bed is well-recognized, the proteome of sPCA remains uncharacterized. Since the porcine ocular system closely resembles that of the human’s and is increasingly employed in translational ophthalmic research, this study characterized the proteome of porcine sPCA employing the mass spectrometry-based proteomics strategy. A total of 1742 proteins and 10527 peptides were identified in the porcine sPCA. The major biological processes involved in the maintenance of physiological functions of the sPCA included redox and metabolic processes, and cytoskeleton organization. These proteins were further clustered into diverse signalling pathways that regulate vasoactivity of sPCA, namely the tight junction, α- and β-adrenoceptor, 14-3-3, nitric oxide synthase and endothelin-1 -mediated signalling pathways. This study provides the first insight into the complex mechanisms dictating the vast protein repertoire in normal vascular physiology of the porcine sPCA. It is envisioned that our findings will serve as important benchmarks for future studies of sPCA.

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“…Another transmembrane receptor‐tyrosine kinase ErbB2 (avian erythroblastosis oncogene B homolog 2), also known as Her2/Neu (human epidermal growth factor receptor 2/protooncogene neu), is ubiquitinated and degraded by proteasome upon exposure to Hsp90 inhibitors geldanamycin and apigenin . Rho GTPases are crucial regulatory proteins, which monitor multiple signaling pathways associated with cellular polarity, organism development, and immune response . Degradation of these proteins is very essential for the fine‐tuning of the immune responses mounted by them on exposure to pathogenic toxins .…”

Section: Proteasome System: Ubiquitin‐dependent Important Mechanisticmentioning

confidence: 99%

“…141,142 Rho GTPases are crucial regulatory proteins, which monitor multiple signaling pathways associated with cellular polarity, organism development, and immune response. 143 Degradation of these proteins is very essential for the fine-tuning of the immune responses mounted by them on exposure to pathogenic toxins. 144 Fine-tuning of TGF-(transforming growth factor-) signaling is also very crucial during developmental periods, and their regulation is largely dependent on Smad (small mothers against decapentaplegic) TFs, which are ubiquitinated and degraded by UPS.…”

Section: Emerging Role Of Proteasome In Cellular Signalingmentioning

confidence: 99%

Proteasome‐mediated proteostasis: Novel medicinal and pharmacological strategies for diseases

Mishra

Upadhyay

Prajapati

et al. 2018

Medicinal Research Reviews

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Proteins actively participate in a wide range of cellular physiological functions. But aggregation of proteins results in cytotoxicity, and unwanted aggregation of misfolded proteins often causes many diseases. During abnormal protein aggregation events, cells try to cope against such deleterious consequences because of the remarkable functional attempts of two distinct proteolytic mechanisms. These tightly regulative and signaling mechanisms are autophagy pathway and ubiquitin proteasome system. Proteasome complex system holds the elimination capacity of intracellular aberrant protein aggregation. Despite the considerable progress that has been achieved, which elucidates wide function and diverse roles of proteasome system, still several crucial problems remain unanswered. For example, how the complex proteasomes assembly and their interactive pathways determine the precise sense of several proteotoxic insults, which can severely affect the cell survival and homeostasis? The specific degradation of various aberrant proteins that can disturb cellular homeostasis is achieved by proper proteasome functionality, which is yet another unclear and critical challenge. Therefore, a better understanding of the various cellular signaling mechanisms composing the proteasome machinery carries broad therapeutic implications linked with proteopathies. This article signifies the urgent need, which is now crucial for us to improve our understanding of the proteasome architecture, structure, and functions that span multiple level strategies from the molecular level to the cellular level. This systematic in-depth information of proteasome may be helpful in the near future to design a new molecular framework based on intrinsic and extrinsic cellular mechanisms that drive the assembly of proteasome to induce cellular survival against proteostasis imbalance and disease conditions.

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Rho GTPases at the crossroad of signaling networks in mammals

Cited by 27 publications

References 40 publications

SIRT5 as a biomarker for response to anthracycline-taxane-based neoadjuvant chemotherapy in triple-negative breast cancer

SIRT5 as a biomarker for response to anthracycline-taxane-based neoadjuvant chemotherapy in triple-negative breast cancer

First insight into the proteome landscape of the porcine short posterior ciliary arteries: Key signalling pathways maintaining physiologic functions

Proteasome‐mediated proteostasis: Novel medicinal and pharmacological strategies for diseases

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