Document Detail

Autophagy is activated, but is not required for the G0 function of BCL-2 or BCL-xL.
MedLine Citation:
PMID:  18758240     Owner:  NLM     Status:  MEDLINE    
Cell cycle arrest in G(0) and autophagy have features in common, but the inter-relationship between the two processes is not well defined. The anti-apoptosis molecules BCL-2 and BCL-x(L) promote G(0) arrest through upregulation of p27 protein, which can also induce autophagy. We tested the hypothesis that autophagy was involved in the cell cycle arrest function of BCL-2 and BCL-x(L). We found that in IL-3-dependent FL5.12 cells, NIH3T3 cells and mouse embryo fibroblasts induced to arrest, treatment with 3-methyladenine did not affect the expected decrease in cell size and ribosomal RNA synthesis, or upregulation of p27 levels. Using the m5-7 ATG5(-/-) MEF cell line with doxycycline-regulated ATG5 expression, we demonstrated that autophagy was activated during serum withdrawal and contact inhibition, but inhibition of autophagy had no measurable effect on G(0) arrest in parental or BCL-x(L)-expressing cells. Thus, our data indicate that, in cell culture models, autophagy occurs but is not required for entrance into quiescence or for the G(0) function of BCL-2 or BCL-x(L).
Mayda Valentin; Elizabeth Yang
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-09-12
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  7     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-04     Completed Date:  2008-10-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2762-8     Citation Subset:  IM    
Departments of Cancer Biology and Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
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MeSH Terms
Adenine / analogs & derivatives,  pharmacology
Autophagy* / drug effects
CHO Cells
Cell Size / drug effects
Cyclin-Dependent Kinase Inhibitor p27 / metabolism
Fibroblasts / cytology*,  drug effects
G0 Phase* / drug effects
Microtubule-Associated Proteins / metabolism
NIH 3T3 Cells
RNA / metabolism
Up-Regulation / drug effects
bcl-X Protein / metabolism*
Grant Support
Reg. No./Substance:
0/Atg5 protein, mouse; 0/Microtubule-Associated Proteins; 0/bcl-X Protein; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 5142-23-4/3-methyladenine; 63231-63-0/RNA; 73-24-5/Adenine

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