Targeting the Small GTPase Superfamily through Their Regulatory Proteins

Gray, Janine L.; Delft, Frank von; Brennan, P.E.

doi:10.1002/anie.201900585

Cited by 109 publications

(93 citation statements)

References 178 publications

(248 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rab proteins cycle between a GDP‐bound inactive state, that is normally cytosolic, and a membrane‐associated GTP‐bound, active conformation 45 . It has been proposed that GDIs retrieve membrane‐bound Rab GTPases to form inactive cytosolic complexes, thus, preventing the dissociation of GDP and subsequent activation of Rab proteins, or their interaction with effector membranes 46,47 …”

Section: Discussionmentioning

confidence: 99%

Adipose tissue depot‐specific intracellular and extracellular cues contributing to insulin resistance in obese individuals

et al. 2020

View full text Add to dashboard Cite

Adipose tissue dysregulation in obesity strongly influences systemic metabolic homeostasis and is often linked to insulin resistance (IR). However, the molecular mechanisms underlying adipose tissue dysfunction in obesity are not fully understood. Herein, a proteomic analysis of subcutaneous (SC) and omental (OM) fat from lean subjects and obese individuals with different degrees of insulin sensitivity was performed to identify adipose tissue biomarkers related to obesity‐associated metabolic disease. Our results suggest that dysregulation of both adipose tissue extracellular matrix (ECM) organization and intracellular trafficking processes may be associated with IR in obesity. Thus, abnormal accumulation of the small leucine‐rich proteoglycan, lumican, as observed in SC fat of IR obese individuals, modifies collagen I organization, impairs adipogenesis and activates stress processes [endoplasmic reticulum and oxidative stress] in adipocytes. In OM fat, IR is associated with increased levels of the negative regulator of the Rab family of small GTPases, GDI2, which alters lipid storage in adipocytes by inhibiting insulin‐stimulated binding of the Rab protein, Rab18, to lipid droplets. Together, these results indicate that lumican and GDI2 might play depot‐dependent, pathogenic roles in obesity‐associated IR. Our findings provide novel insights into the differential maladaptive responses of SC and OM adipose tissue linking obesity to IR.

show abstract

Section: Discussionmentioning

confidence: 99%

Adipose tissue depot‐specific intracellular and extracellular cues contributing to insulin resistance in obese individuals

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The GEFs that control Rho GTPases activation are divided into two families: Dbl and DOCK [ 4 , 69 , 73 ]. In the Dbl family, we can find αPIX, Vav1, Tiam-1, Tiam-2/STEF, RasGRF, Sos1, Dbl, RhoGAP, p115RhoGEF, and Trio.…”

Section: Small Gtpases Of the Rho Familymentioning

confidence: 99%

Small GTPases of the Ras and Rho Families Switch on/off Signaling Pathways in Neurodegenerative Diseases

Sastre

Montoro

Gálvez‐Martín

et al. 2020

IJMS

View full text Add to dashboard Cite

Small guanosine triphosphatases (GTPases) of the Ras superfamily are key regulators of many key cellular events such as proliferation, differentiation, cell cycle regulation, migration, or apoptosis. To control these biological responses, GTPases activity is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and in some small GTPases also guanine nucleotide dissociation inhibitors (GDIs). Moreover, small GTPases transduce signals by their downstream effector molecules. Many studies demonstrate that small GTPases of the Ras family are involved in neurodegeneration processes. Here, in this review, we focus on the signaling pathways controlled by these small protein superfamilies that culminate in neurodegenerative pathologies, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Specifically, we concentrate on the two most studied families of the Ras superfamily: the Ras and Rho families. We summarize the latest findings of small GTPases of the Ras and Rho families in neurodegeneration in order to highlight these small proteins as potential therapeutic targets capable of slowing down different neurodegenerative diseases.

show abstract

“…Rho GTPases have been shown to be difficult to develop drugs against due to their structure, their affinity for GTP and GDP and the high concentration of GTP inside cells (described elsewhere [ 121 , 122 , 123 ]). In addition to their structure, the fact that Rho GTPases are critically involved in numerous processes also adds an additional layer of complexity to successfully targeting Rho GTPases in cancer [ 121 , 124 ].…”

Section: Use Of Rho Gtpases As a Prognostic Tool For Breast Cancermentioning

confidence: 99%

“…In addition to their structure, the fact that Rho GTPases are critically involved in numerous processes also adds an additional layer of complexity to successfully targeting Rho GTPases in cancer [ 121 , 124 ]. Therefore, it is a more reasonable approach to target the activators of Rho GTPases [ 15 , 123 ]. Alternatively, a potential effective clinic use for Rho GTPases is as prognostic biomarkers.…”

Section: Use Of Rho Gtpases As a Prognostic Tool For Breast Cancermentioning

confidence: 99%

Rho GTPases: Big Players in Breast Cancer Initiation, Metastasis and Therapeutic Responses

Humphries

Wang

Yang

2020

Cells

View full text Add to dashboard Cite

Rho GTPases, a family of the Ras GTPase superfamily, are key regulators of the actin cytoskeleton. They were originally thought to primarily affect cell migration and invasion; however, recent advances in our understanding of the biology and function of Rho GTPases have demonstrated their diverse roles within the cell, including membrane trafficking, gene transcription, migration, invasion, adhesion, survival and growth. As these processes are critically involved in cancer initiation, metastasis and therapeutic responses, it is not surprising that studies have demonstrated important roles of Rho GTPases in cancer. Although the majority of data indicates an oncogenic role of Rho GTPases, tumor suppressor functions of Rho GTPases have also been revealed, suggesting a context and cell-type specific function for Rho GTPases in cancer. This review aims to summarize recent progresses in our understanding of the regulation and functions of Rho GTPases, specifically in the context of breast cancer. The potential of Rho GTPases as therapeutic targets and prognostic tools for breast cancer patients are also discussed.

show abstract

Targeting the Small GTPase Superfamily through Their Regulatory Proteins

Cited by 109 publications

References 178 publications

Adipose tissue depot‐specific intracellular and extracellular cues contributing to insulin resistance in obese individuals

Adipose tissue depot‐specific intracellular and extracellular cues contributing to insulin resistance in obese individuals

Small GTPases of the Ras and Rho Families Switch on/off Signaling Pathways in Neurodegenerative Diseases

Rho GTPases: Big Players in Breast Cancer Initiation, Metastasis and Therapeutic Responses

Contact Info

Product

Resources

About