title: E2F-1 lacking the transcriptional activity domain induces autophagy.
abstract: 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.
authors: Department of Surgery, James Graham Brown Cancer Center, Louisville, KY, USA.
authors: Aracely
authors: A
authors: Garcia-Garcia
authors: Humberto
authors: H
authors: Rodriguez-Rocha
authors: Michael T
authors: MT
authors: Tseng
authors: Roberto
authors: R
authors: Montes de Oca-Luna
authors: H Sam
authors: HS
authors: Zhou
authors: Kelly M
authors: KM
authors: McMasters
authors: Jorge G
authors: JG
authors: Gomez-Gutierrez
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001343:Autophagy / Q000235:genetics*; D045744:Cell Line, Tumor; D050687:E2F1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000473:pathology; D017434:Protein Structure, Tertiary; D014162:Transfection; D015854:Up-Regulation
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human