کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1963830 1058510 2011 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cyclin D1 regulates p27Kip1 stability in B cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Cyclin D1 regulates p27Kip1 stability in B cells
چکیده انگلیسی

p27Kip1 is a cyclin-dependent kinase inhibitor that plays a critical role in regulating G1/S transition, and whose activity is, in part, regulated through interactions with D-type cyclins. We have generated the BD1-9 cell line, a BaF3 pro-B cells derivative in which cyclin D1 can be induced rapidly and reversibly by ponasterone A. The induction of cyclin D1 expression leads to a targeted p27Kip1 accumulation in both cytoplasmic and nuclear compartments. But, only the p27Kip1 form phosphorylated on serine 10 (pSer10-p27Kip1) accumulates in BD1-9 cells. We found that the binding of cyclin D1 and pSer10-p27Kip1 prevents p27Kip1 degradation by the cytoplasmic Kip1 ubiquitylation-promoting complex (KPC) proteosomic pathway. Importantly, the nuclear CDK2 activity which is crucial for G1/S transition is not altered by p27Kip1 increase. Using siRNA techniques, we revealed that p27Kip1 inhibition does not affect the distribution of BD1-9 cells in the different phases of the cell cycle. Our study demonstrates that aberrant cyclin D1 expression acts as a p27Kip1 trap in B lymphocytes but does not induce p27Kip1 relocation from the nucleus to the cytoplasm and does not modulate the G1/S transition. Since our cellular model mimics what observed in aggressive lymphomas, our data bring new insights into the understanding of their physiopathology.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 23, Issue 1, January 2011, Pages 171–179
نویسندگان
, , ,