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Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors 总被引:1,自引:0,他引:1
Khan N Jeffers M Kumar S Hackett C Boldog F Khramtsov N Qian X Mills E Berghs SC Carey N Finn PW Collins LS Tumber A Ritchie JW Jensen PB Lichenstein HS Sehested M 《The Biochemical journal》2008,409(2):581-589
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Posttranscriptional suppression of proto-oncogene c-fms expression by vigilin in breast cancer 总被引:1,自引:0,他引:1
Woo HH Yi X Lamb T Menzl I Baker T Shapiro DJ Chambers SK 《Molecular and cellular biology》2011,31(1):215-225
cis-acting elements found in 3'-untranslated regions (UTRs) are regulatory signals determining mRNA stability and translational efficiency. By binding a novel non-AU-rich 69-nucleotide (nt) c-fms 3' UTR sequence, we previously identified HuR as a promoter of c-fms proto-oncogene mRNA. We now identify the 69-nt c-fms mRNA 3' UTR sequence as a cellular vigilin target through which vigilin inhibits the expression of c-fms mRNA and protein. Altering association of either vigilin or HuR with c-fms mRNA in vivo reciprocally affected mRNA association with the other protein. Mechanistic studies show that vigilin decreased c-fms mRNA stability. Furthermore, vigilin inhibited c-fms translation. Vigilin suppresses while HuR encourages cellular motility and invasion of breast cancer cells. In summary, we identified a competition for binding the 69-nt sequence, through which vigilin and HuR exert opposing effects on c-fms expression, suggesting a role for vigilin in suppression of breast cancer progression. 相似文献
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Stabilization of Snail by HuR in the process of hydrogen peroxide induced cell migration 总被引:1,自引:0,他引:1
Dong R Lu JG Wang Q He XL Chu YK Ma QJ 《Biochemical and biophysical research communications》2007,356(1):318-321
Snail functions as a key regulator in the induction of a phenotypic change called epithelial to mesenchymal transition (EMT). Aberrant expression of Snail prevails in the onset and development of tumor. Here, we have observed increased expression of Snail under the treatment of hydrogen peroxide (H(2)O(2)). Investigation into the underlying mechanisms revealed that stabilization of Snail mRNA contributes partially to this process. H(2)O(2)-induced the luciferase activity of the reporter construct contains the 3'UTR of Snail. Deletion of the AU-rich elements in the UTR eliminated the response of the reporter to H(2)O(2), suggesting the potential role of HuR in the process. Lowering of endogenous HuR levels through knockdown of HuR by siRNA greatly reduced the inducability and half-life of Snail mRNA, which consequently inhibited the downregulation of E-cadherin by H(2)O(2). Our findings indicate that HuR plays a major role in regulating H(2)O(2)-induced Snail expression by enhancing Snail mRNA stability, which in turn enhances cell migrating ability through repressing expression of E-cadherin. 相似文献
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Abdelmohsen K Pullmann R Lal A Kim HH Galban S Yang X Blethrow JD Walker M Shubert J Gillespie DA Furneaux H Gorospe M 《Molecular cell》2007,25(4):543-557
The RNA binding protein HuR regulates the stability of many target mRNAs. Here, we report that HuR associated with the 3' untranslated region of the mRNA encoding the longevity and stress-response protein SIRT1, stabilized the SIRT1 mRNA, and increased SIRT1 expression levels. Unexpectedly, oxidative stress triggered the dissociation of the [HuR-SIRT1 mRNA] complex, in turn promoting SIRT1 mRNA decay, reducing SIRT1 abundance, and lowering cell survival. The cell cycle checkpoint kinase Chk2 was activated by H(2)O(2), interacted with HuR, and was predicted to phosphorylate HuR at residues S88, S100, and T118. Mutation of these residues revealed a complex pattern of HuR binding, with S100 appearing to be important for [HuR-SIRT1 mRNA] dissociation after H(2)O(2). Our findings demonstrate that HuR regulates SIRT1 expression, underscore functional links between the two stress-response proteins, and implicate Chk2 in these processes. 相似文献
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Giles KM Daly JM Beveridge DJ Thomson AM Voon DC Furneaux HM Jazayeri JA Leedman PJ 《The Journal of biological chemistry》2003,278(5):2937-2946
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The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA
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Isabel Lpez de Silanes Myriam Gorospe Hiroaki Taniguchi Kotb Abdelmohsen Subramanya Srikantan Miguel Alaminos María Berdasco Rocío G. Urdinguio Mario F. Fraga Filipe V. Jacinto Manel Esteller 《Nucleic acids research》2009,37(8):2658-2671