| Silencing of SmgGDS, a Novel mTORC1 Inducer That Binds to RHEBs, Inhibits Malignant Mesothelioma Cell Proliferation. | Silencing of SmgGDS, a Novel mTORC1 Inducer That Binds to RHEBs, Inhibits Malignant Mesothelioma Cell Proliferation.
Sato T, Mukai S, Ikeda H, Mishiro-Sato E, Akao K, Kobayashi T, Hino O, Shimono W, Shibagaki Y, Hattori S, Sekido Y. | 01/29/2022 |
| Mutated RAP1GDS1 causes a new syndrome of dysmorphic feature, intellectual disability & speech delay. | Mutated RAP1GDS1 causes a new syndrome of dysmorphic feature, intellectual disability & speech delay.
Asiri A, Aloyouni E, Umair M, Alyafee Y, Al Tuwaijri A, Alhamoudi KM, Almuzzaini B, Al Baz A, Alwadaani D, Nashabat M, Alfadhel M., Free PMC Article | 04/24/2021 |
| Targeting SmgGDS splicing to lower the protein isoform ratio is effective to inhibit the malignant phenotype generated by small GTPases. | Splice switching an oncogenic ratio of SmgGDS isoforms as a strategy to diminish malignancy.
Brandt AC, McNally L, Lorimer EL, Unger B, Koehn OJ, Suazo KF, Rein L, Szabo A, Tsaih SW, Distefano MD, Flister MJ, Rigo F, McNally MT, Williams CL., Free PMC Article | 07/11/2020 |
| The competitive binding affinities of the small GTPase for SmgGDS-607 and FTase dictate the extent of this inhibition. SmgGDS-607 increases the rate of farnesylation of HRas by enhancing product release from FTase. | The chaperone SmgGDS-607 has a dual role, both activating and inhibiting farnesylation of small GTPases.
García-Torres D, Fierke CA., Free PMC Article | 03/21/2020 |
| SmgGDS-607 completely inhibits RhoA prenylation catalyzed by protein geranylgeranyltransferase I (GGTase-I) in an in vitro radiolabel incorporation assay. SmgGDS-607 inhibits prenylation by binding to and blocking access to the C-terminal tail of the small GTPase (substrate sequestration mechanism) rather than via inhibition of the prenyltransferase activity. | SmgGDS-607 Regulation of RhoA GTPase Prenylation Is Nucleotide-Dependent.
Jennings BC, Lawton AJ, Rizk Z, Fierke CA., Free PMC Article | 04/13/2019 |
| Study reveals a cryptic pocket by which SmgGDS-558 accommodates RhoA prenylation, loosening the structure of Rho when it interacts with SmgGDS, which may enable drug development strategies for targeting SmgGDS and small GTPases. | GEF mechanism revealed by the structure of SmgGDS-558 and farnesylated RhoA complex and its implication for a chaperone mechanism.
Shimizu H, Toma-Fukai S, Kontani K, Katada T, Shimizu T., Free PMC Article | 10/13/2018 |
| a novel nuclear role for SmgGDS in protecting malignant cells from nucleolar stress, thus promoting cell cycle progression and tumorigenesis. | SmgGDS is a transient nucleolar protein that protects cells from nucleolar stress and promotes the cell cycle by regulating DREAM complex gene expression.
Gonyo P, Bergom C, Brandt AC, Tsaih SW, Sun Y, Bigley TM, Lorimer EL, Terhune SS, Rui H, Flister MJ, Long RM, Williams CL., Free PMC Article | 12/23/2017 |
| Data suggest that SmgGDS-558 splice variant exhibits a fold containing tandem copies of armadillo-repeat motifs not present in other guanine nucleotide exchange factors (GEFs); SmgGDS harbors distinct positively and negatively charged regions, both of which play critical roles in binding to RhoA and in GEF activity. (SmgGDS = smg p21 stimulatory GDP exchange protein; RhoA = ras homolog gene family, member A) | Structure-based analysis of the guanine nucleotide exchange factor SmgGDS reveals armadillo-repeat motifs and key regions for activity and GTPase binding.
Shimizu H, Toma-Fukai S, Saijo S, Shimizu N, Kontani K, Katada T, Shimizu T., Free PMC Article | 08/26/2017 |
| Unlike Rap1B, phosphorylation in the polybasic region of Rap1A does not detectably inhibit its prenylation or its binding to SmgGDS-607. | Differences in the Phosphorylation-Dependent Regulation of Prenylation of Rap1A and Rap1B.
Wilson JM, Prokop JW, Lorimer E, Ntantie E, Williams CL., Free PMC Article | 07/1/2017 |
| In addition, a PINK1 mutant, which induced mitochondrial enlargement and had been considered as a Drosophila model of Parkinson's disease (PD), caused fly muscle defects, and the loss of vimar could rescue these defects. Furthermore, we found that the mammalian homolog of Vimar, RAP1GDS1, played a similar role in regulating mitochondrial morphology, suggesting a functional conservation of this GEF member. | Vimar Is a Novel Regulator of Mitochondrial Fission through Miro.
Ding L, Lei Y, Han Y, Li Y, Ji X, Liu L., Free PMC Article | 04/29/2017 |
| results indicate that statins selectively up-regulate SmgGDS in endothelial cells, for which the beta1-integrin/Akt1 pathway may be involved, demonstrating the novel aspects of the pleiotropic effects of statins | Statins up-regulate SmgGDS through β1-integrin/Akt1 pathway in endothelial cells.
Minami T, Satoh K, Nogi M, Kudo S, Miyata S, Tanaka S, Shimokawa H. | 10/22/2016 |
| DiRas1 expression inhibits malignant features of cancers in part by nonproductively binding to SmgGDS and inhibiting the binding of other small GTPases to SmgGDS | The Tumor-suppressive Small GTPase DiRas1 Binds the Noncanonical Guanine Nucleotide Exchange Factor SmgGDS and Antagonizes SmgGDS Interactions with Oncogenic Small GTPases.
Bergom C, Hauser AD, Rymaszewski A, Gonyo P, Prokop JW, Jennings BC, Lawton AJ, Frei A, Lorimer EL, Aguilera-Barrantes I, Mackinnon AC, Noon K, Fierke CA, Williams CL., Free PMC Article | 08/13/2016 |
| SmgGDS promotes cell cycle progression in multiple types of cancer, making SmgGDS a valuable target for cancer therapeutics. | SmgGDS-558 regulates the cell cycle in pancreatic, non-small cell lung, and breast cancers.
Schuld NJ, Hauser AD, Gastonguay AJ, Wilson JM, Lorimer EL, Williams CL., Free PMC Article | 10/25/2014 |
| TG2 contributes to apoptosis induction in Jurkat T cells by modulating Ca2+ homeostasis via cross-linking RAP1GDS1. | Transglutaminase 2 contributes to apoptosis induction in Jurkat T cells by modulating Ca2+ homeostasis via cross-linking RAP1GDS1.
Hsieh YF, Liu GY, Lee YJ, Yang JJ, Sándor K, Sarang Z, Bononi A, Pinton P, Tretter L, Szondy Z, Tsay GJ., Free PMC Article | 10/4/2014 |
| findings identify SmgGDS-558 as an activator of RhoA and NF-kB in breast cancer, and demonstrate a functional role for SmgGDS-558 in the proliferation of breast cancer cells and tumorigenesis. | The SmgGDS splice variant SmgGDS-558 is a key promoter of tumor growth and RhoA signaling in breast cancer.
Hauser AD, Bergom C, Schuld NJ, Chen X, Lorimer EL, Huang J, Mackinnon AC, Williams CL., Free PMC Article | 10/4/2014 |
| this study provides evidence that SmgGDS-607 associates with GTPases through recognition of the last amino acid in the CAAX motif. | The chaperone protein SmgGDS interacts with small GTPases entering the prenylation pathway by recognizing the last amino acid in the CAAX motif.
Schuld NJ, Vervacke JS, Lorimer EL, Simon NC, Hauser AD, Barbieri JT, Distefano MD, Williams CL., Free PMC Article | 06/28/2014 |
| These results indicate that statins exert their pleiotropic effects through SmgGDS upregulation with a resultant Rac1 degradation and reduced oxidative stress in animals and humans. | Statins exert the pleiotropic effects through small GTP-binding protein dissociation stimulator upregulation with a resultant Rac1 degradation.
Tanaka S, Fukumoto Y, Nochioka K, Minami T, Kudo S, Shiba N, Takai Y, Williams CL, Liao JK, Shimokawa H., Free PMC Article | 08/31/2013 |
| findings provide compelling evidence of a novel role for junctional adhesion molecule-A (JAM-A)in driving breast cancer cell migration via activation of Rap1 GTPase and beta1-integrin | Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPase.
McSherry EA, Brennan K, Hudson L, Hill AD, Hopkins AM., Free PMC Article | 05/26/2012 |
| Results indicate that SmgGDS is a bona fide GEF that specifically activates RhoA and RhoC through a unique mechanism not used by other Rho family exchange factors. | SmgGDS is a guanine nucleotide exchange factor that specifically activates RhoA and RhoC.
Hamel B, Monaghan-Benson E, Rojas RJ, Temple BR, Marston DJ, Burridge K, Sondek J., Free PMC Article | 07/23/2011 |
| Results indicate that guanine nucleotide exchange and interactions with SmgGDS splice variants can regulate the entrance and passage of PBR-possessing small GTPases through the prenylation pathway. | Splice variants of SmgGDS control small GTPase prenylation and membrane localization.
Berg TJ, Gastonguay AJ, Lorimer EL, Kuhnmuench JR, Li R, Fields AP, Williams CL., Free PMC Article | 02/26/2011 |
| C3G stimulates guanine nucleotide exchange on Drosophila Rap GTPases in vitro | The Rap1 guanine nucleotide exchange factor C3G is required for preservation of larval muscle integrity in Drosophila melanogaster.
Shirinian M, Popovic M, Grabbe C, Varshney G, Hugosson F, Bos H, Rehmann H, Palmer RH., Free PMC Article | 01/15/2011 |
| ALK activation of Rap1 via the Rap1-specific GEF C3Gmay contribute to cell proliferation and oncogenesis of neuroblastoma. | Anaplastic lymphoma kinase activates the small GTPase Rap1 via the Rap1-specific GEF C3G in both neuroblastoma and PC12 cells.
Schönherr C, Yang HL, Vigny M, Palmer RH, Hallberg B. | 06/14/2010 |
| Epac activates the small G proteins Rap1 and Rab3A to achieve exocytosis. | Epac activates the small G proteins Rap1 and Rab3A to achieve exocytosis.
Branham MT, Bustos MA, De Blas GA, Rehmann H, Zarelli VE, Treviño CL, Darszon A, Mayorga LS, Tomes CN., Free PMC Article | 01/21/2010 |
| Observational study and genome-wide association study of gene-disease association. (HuGE Navigator) | Genome-wide association study of biochemical traits in Korcula Island, Croatia.
Zemunik T, Boban M, Lauc G, Janković S, Rotim K, Vatavuk Z, Bencić G, Dogas Z, Boraska V, Torlak V, Susac J, Zobić I, Rudan D, Pulanić D, Modun D, Mudnić I, Gunjaca G, Budimir D, Hayward C, Vitart V, Wright AF, Campbell H, Rudan I., Free PMC Article | 03/25/2009 |
| SmgGDS promotes the malignant Non-small cell lung carcinoma (NSCLC)phenotype and is an intriguing therapeutic target in NSCLC. | SmgGDS regulates cell proliferation, migration, and NF-kappaB transcriptional activity in non-small cell lung carcinoma.
Tew GW, Lorimer EL, Berg TJ, Zhi H, Li R, Williams CL. | 01/21/2010 |