Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ARHI (aplasia Ras homologue member I; also known as DIRAS3) is an imprinted tumour suppressor gene, the expression of which is lost in the majority of breast and ovarian cancers. Unlike its homologues Ras and Rap, ARHI functions as a tumour suppressor. Our previous study showed that ARHI can interact with the transcriptional activator STAT3 (signal transducer and activator of transcription 3) and inhibit its nuclear translocation in human breast- and ovarian-cancer cells. To identify proteins that interact with ARHI in nuclear translocation, in the present study, we performed proteomic analysis and identified several importins that can associate with ARHI. To further explore this novel finding, we purified 10 GST (glutathione transferase)-importin fusion proteins (importins 7, 8, 13, beta1, alpha1, alpha3, alpha5, alpha6, alpha7 and mutant alpha1). Using a GST-pulldown assay, we found that ARHI can bind strongly to most importins; however, its binding is markedly reduced with an importin alpha1 mutant that contains an altered NLS (nuclear-localization signal) domain. In addition, an ARHI N-terminal deletion mutant exhibits greatly reduced binding to all importins compared with wild-type ARHI. In nuclear-import assays, the addition of ARHI blocked nuclear localization of phosphorylated STAT3. ARHI also inhibits the interaction of Ran-importin complexes with GFP (green fluorescent protein) fusion proteins that contain an NLS domain and a beta-like import receptor-binding domain, thereby blocking their nuclear localization. By conducting GST-pulldown assays, we found that ARHI could compete for Ran-importin binding. Thus ARHI-induced disruption of importin-binding to cargo proteins, including STAT3, could serve as an important regulatory mechanism that contributes to the tumour-suppressor function of ARHI.
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PMID:ARHI (DIRAS3), an imprinted tumour suppressor gene, binds to importins and blocks nuclear import of cargo proteins. 1943 63

Globally, prostate cancer is the most common malignancy among men and there is no biomarker for defining tumour invasion and progression. Guanosine-5'-triphosphate (GTP)-binding RAS-like 3 (ARHI) is a tumour suppressor gene that has been found to be downregulated in the prostate cancer cell line PC-3. MicroRNA 221 and 222 have been shown to regulate ARHI expression negatively. This study evaluated tissue samples from patients with prostate cancer (n = 35) that were designated as aggressive or non-aggressive according to their Gleason grade. Expression of ARHI and microRNA 221 and 222 was measured by real-time reverse transcription-polymerase chain reaction. The level of ARHI mRNA was significantly lower in aggressive compared with non-aggressive prostate cancer tissue samples. In contrast, microRNA 221 and 222 levels were significantly higher in aggressive compared with non-aggressive prostate cancer tissue samples. Whether ARHI and microRNA 221 and 222 could be considered as biomarkers for disease progression in prostate cancer requires further investigation.
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PMID:The expression and clinical significance of GTP-binding RAS-like 3 (ARHI) and microRNA 221 and 222 in prostate cancer. 2211 88