Similar results were also found in both cell lines in response to blockage of ER stress by silencing of PERK (Fig. 5c).
The regulation of different autophagic pathways is closely interconnected and most cells activate macroautophagy in response to blockage of CMA (Massey et al, 2006a; Kaushik et al, 2008).
By western blot, we further confirmed increased autophagy in U937-B8 cells by observing a greater accumulation of p62 and LC3-II in response to blockage of autophagosome clearance by CQ.
Autophagic pathways are closely interconnected (Park & Cuervo, 2013), and although they are preferentially activated in a time- and stimuli-specific manner, most cells activate macroautophagy in response to blockage of CMA and vice versa (Massey et al, 2006a; Kaushik et al, 2008).
23, 46, 47 In the present study, declines of the levels of the phosphorylation of p70S6K and mTOR induced by AMP were also partially restored in response to blockage of ER stress pathway by 4-BPA and silencing of PERK, suggesting that activation of ER stress induced by AMP was closely linked to inhibition of Akt-mTOR pathway.
Finally, our results indicate that death receptors overexpression might be directly induced by γ-irradiation, whereas the death receptors ligands overexpression might be the consequence of the mitotic catastrophe in response to blockage of cell cycle checkpoints or abnormal mitosis (29).
Together, these data support that macroautophagy compensation in response to CMA blockage is not sustained with age.
Co-immunoprecipitation experiments suggest that WRN and RPA association is enhanced in response to fork blockage inducing-treatments and this interaction is instrumental for the WRN-mediated displacement of RPA from DNA that contributes to fork recovery [ 23].
The observed effects of endocrine treatment on SRC expression in different model systems in vivo suggest that induction of coactivators is an early response to the blockage of ER mediated signaling in breast tissue.
The nature of Nbs1-deficient primary neuron was verified by the lack of Mre11 and Rad50 foci, and Mre11 retained in the cytoplasm in the absence of Nbs1 in response to replication blockage.
