The RB-E2F1 pathway regulates autophagy.
The RB-E2F1 pathway regulates autophagy.
复制标题
DOI：
10.1158/0008-5472.can-10-1604
复制
发表时间：
2010-10-15
期刊：
影响因子：
11.2
通讯作者：
Fueyo J
中科院分区：
文献类型：
--
作者：
Jiang H;Martin V;Gomez-Manzano C;Johnson DG;Alonso M;White E;Xu J;McDonnell TJ;Shinojima N;Fueyo J
自噬是一种保护机制，使细胞在应激条件下存活。新出现的证据表明，这一细胞过程也是一种肿瘤抑制途径。以往的研究表明，细胞周期蛋白依赖性激酶抑制剂（CDKI）诱导自噬。视网膜母细胞瘤蛋白（RB），一个关键的肿瘤抑制因子和下游靶点的CDKIs，是否诱导自噬尚不清楚。在这里，我们表明，RB触发自噬和RB激活剂p16 INK 4a和p27/kip 1诱导自噬在RB依赖的方式。RB与E2转录因子（E2 F）的结合是自噬诱导所必需的，E2 F1拮抗RB诱导的自噬，导致细胞凋亡。细胞中E2 F1的下调导致高水平的自噬。我们的研究结果表明RB通过抑制E2 F1活性诱导自噬。我们推测RB功能的这一新发现的方面与癌症的发展和治疗有关。
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 (CDKI) induce autophagy. Whether retinoblastoma protein (RB), a key tumor suppressor and downstream target of CDKIs, induces autophagy is not clear. Here, we show that RB triggers autophagy and that the RB activators p16INK4a and p27/kip1 induce autophagy in an RB-dependent manner. RB binding to E2 transcription factor (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 findings 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.