Cmejla Radek, Petrak Jiri, Cmejlova Jana
Institute of Hematology and Blood Transfusion, Department of Cell Physiology, U Nemocnice 1, Prague, Czech Republic.
Biochem Biophys Res Commun. 2006 Mar 3;341(1):158-66. doi: 10.1016/j.bbrc.2005.12.155. Epub 2006 Jan 6.
Human untranslated region (UTR) databases were searched to identify novel proteins potentially regulated by an iron responsive element (IRE), and found two candidates-cell cycle phosphatase Cdc14A variant 1 and myotonic dystrophy kinase-related Cdc42-binding kinase alpha (MRCKalpha), both possessing a putative IRE in their 3'UTR. In further experiments, we focused on MRCKalpha. Biochemical analyses of the MRCKalpha IRE revealed that it was functional and mediated the response to iron level in the same way as transferrin receptor 1 IREs (TfR) did. Similarly to TfR mRNA, MRCKalpha mRNA is stabilized, when iron supply is low, while it is destabilized under iron-rich conditions. The expression of MRCKalpha mRNA was found to be ubiquitous; the highest levels were noted in testes, the lowest in skeletal muscle. The level of MRCKalpha mRNA in various tissues strongly positively correlates with the level of TfR mRNA, indicating its possible role in the transferrin iron uptake pathway.
检索人类非翻译区(UTR)数据库,以识别可能受铁反应元件(IRE)调控的新型蛋白质,发现了两个候选蛋白——细胞周期磷酸酶Cdc14A变体1和强直性肌营养不良激酶相关的Cdc42结合激酶α(MRCKα),二者在其3'UTR中均具有一个假定的IRE。在进一步的实验中,我们聚焦于MRCKα。对MRCKα IRE的生化分析表明,它具有功能,并且介导对铁水平的反应,其方式与转铁蛋白受体1 IRE(TfR)相同。与TfR mRNA类似,当铁供应不足时,MRCKα mRNA会稳定,而在铁充足的条件下则会不稳定。发现MRCKα mRNA的表达普遍存在;在睾丸中水平最高,在骨骼肌中最低。各种组织中MRCKα mRNA的水平与TfR mRNA的水平呈强烈正相关,表明其在转铁蛋白铁摄取途径中可能发挥的作用。