p53 and p21(Waf1) are recruited to distinct PML-containing nuclear foci in irradiated and Nutlin-3a-treated U2OS cells.
p53 and p21(Waf1) are recruited to distinct PML-containing nuclear foci in irradiated and Nutlin-3a-treated U2OS cells.
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DOI：
10.1002/jcb.22852
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发表时间：
2010-12-01
影响因子：
4
通讯作者：
Maki, Carl G.
中科院分区：
文献类型：
--
作者：
Shen, Hong;Maki, Carl G.
Promyelocytic leukemia nuclear bodies (PML-NBs) are multi-protein complexes that include PML protein and localize in nuclear foci. PML-NBs are implicated in multiple stress responses, including apoptosis, DNA repair, and p53-dependent growth inhibition. ALT-associated PML bodies (APBs) are specialized PML-NBs that include telomere-repeat binding-factor TRF1 and are exclusively in telomerase-negative tumors where telomere length is maintained through alternative (ALT) recombination mechanisms. We compared cell cycle and p53 responses in ALT-positive cancer cells (U2OS) exposed to ionizing radiation (IR) or the p53 stabilizer Nutlin-3a. Both IR and Nutlin-3a caused growth arrest and comparable induction of p53. However, p21, whose gene p53 activates, displayed biphasic induction following IR and monophasic induction following Nutlin-3a. P53 was recruited to PML-NBs 3–4 days after IR, approximately coincident with the secondary p21 increase. These p53/PML-NBs marked sites of apparently unrepaired DNA double-strand breaks (DSBs), identified by colocalization with phosphorylated histone H2AX. Nutlin-3a and IR both caused a large increase in APBs that was dependent on p53 and p21 expression. Moreover, p21, and to a lesser extent p53, was recruited to APBs in a fraction of Nutlin-3a treated cells. These data indicate 1) p53 is recruited to PML-NBs after IR that likely mark unrepaired DSBs, suggesting p53 may either be further activated at these sites and/or function in their repair; 2) p53-p21 pathway activation increases the percentage of APB-positive cells, 3) p21 and p53 are recruited to ALT-associated PML-NBs after Nutlin-3a treatment, suggesting they may play a previously unrecognized role in telomere maintenance.
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影响因子：
8
作者：
Carbone, R;Pearson, M;Pelicci, PG
通讯作者：
Pelicci, PG
影响因子：
11.4
作者：
Fogal, V;Gostissa, M;Del Sal, G
通讯作者：
Del Sal, G
DOI：
10.1073/pnas.0907689106
发表时间：
2009-09-15
影响因子：
11.1
作者：
Draskovic, Irena;Arnoult, Nausica;Londono-Vallejo, Arturo
通讯作者：
Londono-Vallejo, Arturo
影响因子：
11.2
作者：
Fasching, Clare L.;Neumann, Axel A.;Reddel, Roger R.
通讯作者：
Reddel, Roger R.
影响因子：
56.9
作者：
GODDARD, AD;BORROW, J;SOLOMON, E
通讯作者：
SOLOMON, E