کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8324216 | 1539907 | 2013 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The Bcl-2/Bcl-xL inhibitor BH3I-2â² affects the dynamics and subcellular localization of sumoylated proteins
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: The Bcl-2/Bcl-xL inhibitor BH3I-2â² affects the dynamics and subcellular localization of sumoylated proteins The Bcl-2/Bcl-xL inhibitor BH3I-2â² affects the dynamics and subcellular localization of sumoylated proteins](/preview/png/8324216.png)
چکیده انگلیسی
Sumoylation modulates many proteins implicated in apoptosis such as Fas, TNFR1, Daxx, p53 and its regulator MDM2. Some of these proteins, such as DRP-1, are involved in the intrinsic apoptosis pathway. The intrinsic pathway is regulated at the mitochondrial level by the Bcl-2 family of proteins. The small-molecule inhibitor BH3I-2â² binds to the hydrophobic groove of the BH3 domain of anti-apoptotic proteins Bcl-xL and Bcl-2. Following treatment with this inhibitor in various experimental conditions, we observed decreased levels of detergent-soluble SUMO-1, an increase in the relative levels of detergent-insoluble sumoylated proteins, or both. Accordingly, immunofluorescence microscopy revealed that the relative numbers and intensities of endogenously or exogenously expressed SUMO-1 foci in the nucleus were increased following BH3I-2â² treatment. MG132 caused a large increase in steady-state levels of SUMO-1 and of sumoylated proteins, and this was especially true for detergent-insoluble proteins. The conjugation-incompetent GG-to-AA SUMO-1 mutant, which did not form nuclear foci, was only present in the detergent-soluble lysate fraction and was insensitive to BH3I-2â², implying that BH3I-2â² specifically affects SUMO in its conjugated form. Finally, BH3I-2â² had similar effects on SUMO-2 and SUMO-3 as it had on SUMO-1. In conclusion, BH3I-2â² causes an intracellular redistribution of sumoylated proteins, more specifically their targeting to PML and non-PML nuclear bodies in which they may be degraded by the proteasome. Interestingly, knocking down Bcl-2 also altered levels of sumoylated proteins and their presence in detergent-insoluble compartments, confirming the role of Bcl-2 as a modulator of the sumoylation pathway.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 45, Issue 4, April 2013, Pages 826-835
Journal: The International Journal of Biochemistry & Cell Biology - Volume 45, Issue 4, April 2013, Pages 826-835
نویسندگان
Mélodie B. Plourde, Aïda Morchid, Lolita Iranezereza, Lionel Berthoux,