Rho regulation: DLC proteins in space and time

Braun, Anja C.; Olayioye, Monilola A.

doi:10.1016/j.cellsig.2015.04.003

Cited by 67 publications

(62 citation statements)

References 99 publications

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“…We focused on an apparently paradoxical result of our screen that is centered around RhoA and two RhoA-specific GAPs: ARH GAP5 (p190RhoGAP; Ridley et al, 1993;Arthur and Burridge, 2001) and DLC1 (deleted in liver cancer; Kim et al, 2009;Braun and Olayioye, 2015). Consistently with the classic model (Hirose et al, 1998), we observed that RhoA KD led to longer neurites, which results in decreased neurite collapse events (Fig.…”

Section: Spatiotemporal Regulation Of Rhoa Activation By Two Rhoa-spesupporting

confidence: 51%

Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling

Fusco¹,

Lefort²,

Smith³

et al. 2016

J Exp Med

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Abbreviations used in this paper: CV, computer vision; FRET, Förster resonance energy transfer; GAP, GTPase-activating protein; GEF, guanine nucleotide-exchange factor; HDS, hierarchical data structure; HS, high stringency; KD, knockdown; LS, low stringency; MDS, morphodynamic signature; MLCK, myosin light chain kinase; MP, morphogenetic process; MRCK, myotonin-related dystrophyn kinase myosin light chain kinase; pMLC, myosin light chain phosphorylation.

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Section: Spatiotemporal Regulation Of Rhoa Activation By Two Rhoa-spesupporting

confidence: 51%

Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling

Fusco¹,

Lefort²,

Smith³

et al. 2016

J Exp Med

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“…This regulation mechanism is common to all DLC family members of RHO GTP-ases and different identified isoforms of DLC2 ( STARD13 ) and DLC3 ( STARD8 ) are transcribed from alternative promoters. DLC-1 isoforms, except from DLC1-v3 [7], encode functional RHO GTPases that differ in N-terminal region and share the same functional domains [3]. It seems that they differ in subcellular localization.…”

Section: Discussionmentioning

confidence: 99%

“…These proteins act as molecular switches through the regulation of small GTP-binding proteins. RhoGAPs take part in cell signaling and are involved in regulating a variety of cellular proteins [3]. …”

Section: Introductionmentioning

confidence: 99%

Aberrant DNA methylation of alternative promoter of DLC1 isoform 1 in meningiomas

et al. 2016

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DLC1 encodes GTPase-activating protein with a well-documented tumor suppressor activity. This gene is downregulated in various tumors through aberrant promoter hypermethylation. Five different DLC1 isoforms can be transcribed from alternative promoters. Tumor-related DNA methylation of the DLC1 isoform 1 alternative promoter was identified as being hypermethylated in meningiomas in genome-wide DNA methylation profiling. We determined the methylation pattern of this region in 50 meningioma FFPE samples and sections of 6 normal meninges, with targeted bisulfite sequencing. All histopathological subtypes of meningiomas showed similar and significant increase of DNA methylation levels. High DNA methylation was associated with lack of DLC1 protein expression in meningiomas as determined by immunohistochemistry. mRNA expression levels of 5 isoforms of DLC1 transcript were measured in an additional series of meningiomas and normal meninges. The DLC1 isoform 1 was found as the most expressed in normal control tissue and was significantly downregulated in meningiomas. Transfection of KT21 meningioma cell line with shRNA targeting DLC1 isoform 1 resulted in increased activation of RHO-GTPases assessed with pull-down assay, enhanced cell migration observed in scratch assay as well as slight increase of cell metabolism determind by MTT test. Results indicate that isoform 1 represents the main pool of DLC1 protein in meninges and its downregulation in meningiomas is associated with hypermethylation of CpG dinucleotides within the corresponding promoter region. This isoform is functional GAP protein and tumor suppressor and targeting of its expression results in the increase of DLC1 related cell processes: RHO activation and cell migration.

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“…59 The same is true for the activation of Rho proteins which require a distinct localization of a particular Rho-GEF and a halo of a particular Rho-GAP around the area of activation, in order to induce locally defined and directed membrane deformations such as neurite protrusions or filopodia. 60 A good example of temporal hierarchical regulation of the GTPase cycle has been demonstrated for the entry of Salmonella typhimurium into cells. The bacterium first injects, via the type III secretion system the Rho-GEF SopE into cell to activate actin remodeling and later injects the Rho-GAP SptP to finish the uptake.…”

Section: Resultsmentioning

confidence: 99%