The RB-E2F1 Pathway Regulates Autophagy.
Summary of "The RB-E2F1 Pathway Regulates Autophagy."
Autophagy is a protective mechanism that renders cells viable in stressful conditions. Emerging evidence suggests that this cellular process is also a tumor suppressor pathway. Previous studies showed that cyclin-dependent kinase inhibitors (CDKIs) induce autophagy. Whether retinoblastoma protein (RB), a key tumor suppressor and downstream target of CDKIs, induces autophagy is not clear. Here we first demonstrate that RB triggers autophagy and that the RB activators p16INK4a and p27/kip1 induce autophagy in an RB-dependent manner. RB binding to E2F is required for autophagy induction and E2F1 antagonizes RB-induced autophagy, leading to apoptosis. Downregulation of E2F1 in cells results in high levels of autophagy. Our findnigs indicate that RB induces autophagy by repressing E2F1 activity. We speculate that this newly discovered aspect of RB function is relevant to cancer development and therapy.
Affiliation
Neuro-Oncology, UT M. D. Anderson Cancer Center.
Journal Details
This article was published in the following journal.
Name: Cancer research
ISSN: 1538-7445
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20807803
- DOI: http://dx.doi.org/10.1158/0008-5472.CAN-10-1604
Medical and Biotech [MESH] Definitions
E2f1 Transcription Factor
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.
Complement C4b-binding Protein
A serum protein that regulates the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE (C4bC2a).
Perforant Pathway
A pathway of fibers that originates in the lateral part of the ENTORHINAL CORTEX, perforates the SUBICULUM of the HIPPOCAMPUS, and runs into the stratum moleculare of the hippocampus, where these fibers synapse with others that go to the DENTATE GYRUS where the pathway terminates. It is also known as the perforating fasciculus.
Autophagy
The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.
Complement System Proteins
Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).
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