DIRAS1

Last update 08 May 2025

Basic Info

Synonyms

Di-Ras1, DIRAS family GTPase 1, DIRAS1

+ [6]

Introduction

Displays low GTPase activity and exists predominantly in the GTP-bound form.

100 Clinical Results associated with DIRAS1

100 Translational Medicine associated with DIRAS1

0 Patents (Medical) associated with DIRAS1

Literatures (Medical) associated with DIRAS1

31 Dec 2024·Cancer Biology & Therapy

M6A modification regulates tumor suppressor DIRAS1 expression in cervical cancer cells

Article

Author: Wang, Yu-Yan ; Dai, Ning ; Zhang, Xin ; Gao, Wei-Ran ; Ye, Lian-Hua ; Yin, Yu ; Zhao, An-Qi

DIRAS family GTPase 1 (DIRAS1) has been reported as a potential tumor suppressor in other human cancer. However, its expression pattern and role in cervical cancer remain unknown. Knockdown of DIRAS1 significantly promoted the proliferation, growth, migration, and invasion of C33A and SiHa cells cultured in vitro. Overexpression of DIRAS1 significantly inhibited the viability and motility of C33A and SiHa cells. Compared with normal cervical tissues, DIRAS1 mRNA levels were significantly lower in cervical cancer tissues. DIRAS1 protein expression was also significantly reduced in cervical cancer tissues compared with para-cancerous tissues. In addition, DIRAS1 expression level in tumor tissues was significantly negatively correlated with the pathological grades of cervical cancer patients. DNA methylation inhibitor (5-Azacytidine) and histone deacetylation inhibitor (SAHA) resulted in a significant increase in DIRAS1 mRNA levels in C33A and SiHa cells, but did not affect DIRAS1 protein levels. FTO inhibitor (FB23-2) significantly down-regulated intracellular DIRAS1 mRNA levels, but significantly up-regulated DIRAS1 protein levels. Moreover, the down-regulation of METTL3 and METTL14 expression significantly inhibited DIRAS1 protein expression, whereas the down-regulation of FTO and ALKBH5 expression significantly increased DIRAS1 protein expression. In conclusion, DIRAS1 exerts a significant anti-oncogenic function and its expression is significantly downregulated in cervical cancer cells. The m6A modification may be a key mechanism to regulate DIRAS1 mRNA stability and protein translation efficiency in cervical cancer.

01 Dec 2024·Alzheimer's & Dementia

Identifying partial haplotypes that are associated with late‐onset Alzheimer disease

Article

Author: Climer, Sharlee

AbstractBackgroundHaplotypes are patterns of nucleotides in close proximity along a chromosome that are passed together across time and space. These patterns dictate the specific properties of proteins produced and the regulation of this production. General haplotype inference methods phase all provided genotypes within the region of interest into two haplotypes without regard for the ages or evolutionary impact of each mutation, thus force the inclusion of more recent and/or neutral mutations. Alternatively, BlocBuster (www.blocbuster.org) identifies partial haplotypes that include only highly correlated nucleotides using a unique correlation metric that anticipates heterogeneity of the individuals and an expanded network scaffolding. Given the heterogeneous nature of late‐onset Alzheimer disease (AD), we utilize BlocBuster to identify genetic risk patterns.MethodWe analyzed WGS_Omni2.5M_20140220 data for chromosome 19 provided in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database(adni.loni.usc.edu). The data were arbitrarily split into 70% Discovery (42 AD, 69 MCI, 87 control) and 30% Validation (18 AD, 29 MCI, 37 control). BlocBuster builds a network model using AD, MCI, and control individuals (without labeling), where nodes represent SNP alleles and edges represent pairwise correlations between alleles, extracts clusters of inter‐correlated SNP alleles representing a partial haplotype, then tests the pattern for association with the given phenotype.ResultBlocBuster identified two patterns that are significantly associated with AD in both the Discovery and the independent Validation datasets(Table 1). The first represents a variant of the RUVBL2 gene and the second is a large allelic combination beginning upstream from DIRAS1 and spanning across SLC39A3, SGTA, and THOP1(Table 2).ConclusionThe network model was created blindly using all individuals in the Discovery dataset, yet two of the clusters were significantly associated with AD risk in both the Discovery and Validation data. Interestingly, THOP1 is a zinc‐activated oligopeptidase that is capable of cleaving beta‐amyloid precursor protein into amyloidogenic peptides. Furthermore, SLC39A3 is predicted to enable zinc transport across the membrane, SGTA is suggested to play a role in aggregate formation in neurodegenerative diseases, and methylation of DIRAS1 is associated with AD risk. These results identify interesting signatures that may pinpoint specific AD biological pathways, motivating further validation efforts.

01 Jun 2023·The Journal of biological chemistry

GTPase splice variants RAC1 and RAC1B display isoform-specific differences in localization, prenylation, and interaction with the chaperone protein SmgGDS.

Article

Author: Williams, Carol L ; Auger, Shelby A ; Lorimer, Ellen ; Koehn, Olivia J ; Das, Akansha S ; Prokop, Jeremy W ; Harris, Ra'Mal ; Distefano, Mark D ; Unger, Bethany ; Suazo, Kiall F

Identifying events that regulate the prenylation and localization of small GTPases will help define new strategies for therapeutic targeting of these proteins in disorders such as cancer, cardiovascular disease, and neurol. deficits.Splice variants of the chaperone protein SmgGDS (encoded by RAP1GDS1) are known to regulate prenylation and trafficking of small GTPases.The SmgGDS-607 splice variant regulates prenylation by binding preprenylated small GTPases but the effects of SmgGDS binding to the small GTPase RAC1 vs. the splice variant RAC1B are not well defined.Here we report unexpected differences in the prenylation and localization of RAC1 and RAC1B and their binding to SmgGDS.Compared to RAC1, RAC1B more stably associates with SmgGDS-607, is less prenylated, and accumulates more in the nucleus.We show that the small GTPase DIRAS1 inhibits binding of RAC1 and RAC1B to SmgGDS and reduces their prenylation.These results suggest that prenylation of RAC1 and RAC1B is facilitated by binding to SmgGDS-607 but the greater retention of RAC1B by SmgGDS-607 slows RAC1B prenylation.We show that inhibiting RAC1 prenylation by mutating the CAAX motif promotes RAC1 nuclear accumulation, suggesting that differences in prenylation contribute to the different nuclear localization of RAC1 vs. RAC1B.Finally, we demonstrate RAC1 and RAC1B that cannot be prenylated bind GTP in cells, indicating that prenylation is not a prerequisite for activation.We report differential expression of RAC1 and RAC1B transcripts in tissues, consistent with these two splice variants having unique functions that might arise in part from their differences in prenylation and localization.

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DIRAS1

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