کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1985043 | 1539952 | 2009 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Enzymatically inactive adenylate kinase 4 interacts with mitochondrial ADP/ATP translocase
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کلمات کلیدی
P1,P5-Di(Adenosine-5′)PentaphosphateAp5AshRNAVDACSOD1MPTPANTDAPI4′,6-diamidino-2-phenylindole - 4 '، 6-دیامیدینو-2-فنیلینولLC–MS - LC-MSshort hairpin RNA - RNA موی سر کوتاهAdenylate kinase - آدنیلات کینازamyotrophic lateral sclerosis - اسکلروز جانبی آمیوتروفیکmitochondrial permeability transition pore - انتقال نفوذی میتوکندری منفی استCell survival - بقای سلولیALS - بیماری اسکلروز جانبی آمیوتروفیکImmunoprecipitation - تخریب ایمنیMass spectrometry - طیف سنجی جرمیEnzymatic activity - فعالیت آنزیمیnucleoside monophosphate kinase - نوکلئوزید مونوفسفات کینازStress response - پاسخ به استرسvoltage dependent anion channel - کانال آنیونی وابسته به ولتاژ
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Adenylate kinase 4 (AK4) is a unique member with no enzymatic activity in vitro in the adenylate kinase (AK) family although it shares high sequence homology with other AKs. It remains unclear what physiological function AK4 might play or why it is enzymatically inactive. In this study, we showed increased AK4 protein levels in cultured cells exposed to hypoxia and in an animal model of the neurodegenerative disease amyotrophic lateral sclerosis. We also showed that short hairpin RNA (shRNA)-mediated knockdown of AK4 in HEK293 cells with high levels of endogenous AK4 resulted in reduced cell proliferation and increased cell death. Furthermore, we found that AK4 over-expression in the neuronal cell line SH-SY5Y with low endogenous levels of AK4 protected cells from H2O2 induced cell death. Proteomic studies revealed that the mitochondrial ADP/ATP translocases (ANTs) interacted with AK4 and higher amount of ANT was co-precipitated with AK4 when cells were exposed to H2O2 treatment. In addition, structural analysis revealed that, while AK4 retains the capability of binding nucleotides, AK4 has a glutamine residue instead of a key arginine residue in the active site well conserved in other AKs. Mutation of the glutamine residue to arginine (Q159R) restored the adenylate kinase activity with GTP as substrate. Collectively, these results indicate that the enzymatically inactive AK4 is a stress responsive protein critical to cell survival and proliferation. It is likely that the interaction with the mitochondrial inner membrane protein ANT is important for AK4 to exert the protective benefits to cells under stress.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 41, Issue 6, June 2009, Pages 1371-1380
Journal: The International Journal of Biochemistry & Cell Biology - Volume 41, Issue 6, June 2009, Pages 1371-1380
نویسندگان
Rujuan Liu, Anna-Lena Ström, Jianjun Zhai, Jozsef Gal, Shilai Bao, Weimin Gong, Haining Zhu,