E2F-1 lacking the transcriptional activity domain induces autophagy

The transcription factor E2F-1 plays a crucial role in the control of cell proliferation. E2F-1 has tumor suppressive properties by inducing apoptosis and autophagy. In this study, E2F-1 and its truncated form (E2Ftr), lacking the transactivation domain (TAD), were compared for their ability to indu...

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Bibliographic Details
Published in:Cancer biology & therapy 2012-09, Vol.13 (11), p.1091-1101
Main Authors: Garcia-Garcia, Aracely, Rodriguez-Rocha, Humberto, Tseng, Michael T., Montes de Oca-Luna, Roberto, Zhou, H. Sam, McMasters, Kelly M., Gomez-Gutierrez, Jorge G.
Format: Article
Language:English
Subjects:
adenovirus
apoptosis
Apoptosis - genetics
autophagy
Autophagy - genetics
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cell Line, Tumor
Cycle
E2F-1
E2F1 Transcription Factor - genetics
E2F1 Transcription Factor - metabolism
E2Ftr
HEK293 Cells
Humans
Landes
melanoma
Melanoma - genetics
Melanoma - pathology
Organogenesis
Protein Structure, Tertiary
Proteins
Research Paper
Transfection
Up-Regulation
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Summary:The transcription factor E2F-1 plays a crucial role in the control of cell proliferation. E2F-1 has tumor suppressive properties by inducing apoptosis and autophagy. In this study, E2F-1 and its truncated form (E2Ftr), lacking the transactivation domain (TAD), were compared for their ability to induce autophagy. In Gaussia luciferase-based assays, both E2F-1 and E2Ftr induced the proteolytic cleavage of the autophagic marker LC3. In addition, LC3 and autophagy protein 5 (Atg5) were upregulated by E2F-1 and E2Ftr. Likewise, both E2F proteins induced a punctate pattern of GFP-tagged LC3, indicating autophagosome formation. The presence of double-membrane autophagic vesicles induced by E2F-1 and E2Ftr was confirmed by transmission electron microscopy (TEM). The application of z-VAD-fmk, a caspase inhibitor, partially blocked both E2F-1 and E2Ftr-mediated cytotoxicity. Moreover, Atg5 −/− cells were more resistant to the E2F-1 or E2Ftr-induced cell killing effect than Atg5 wt cells. The TAD of E2F-1 is not essential for induction of autophagy; apoptosis and autophagy cooperate for an efficient cancer cell killing effect induced by E2F-1 or E2Ftr. E2Ftr-induced autophagy is a promising approach to destroy tumors that are resistant to conventional treatments.
ISSN:1538-4047
1555-8576
DOI:10.4161/cbt.21143