Abstract IA15: The consequences of pRb inactivation: insights from a proteomic analysis of Rb loss

The retinoblastoma tumor suppressor protein associates with chromatin and regulates gene expression. The transcriptional signatures associated with RB1/Rb mutation are thought to give a picture of the cellular changes that occur when pRB is lost. We used proteomic profiling to examine the changes caused by the ablation of Rb in mouse lung and colon tissues, and compared these with transcript profiles. While the transcription of classic E2F target genes increased similarly in Rbko lung and colon, effects on protein levels were context-dependent. Proteomic changes were identified that were similar between Rb-mutant tissues but, unexpectedly, the major feature of these changes was a decrease in proteins that function in mitochondria. Consistent with this, mutation of RB1 in cultured human cells reduced the number of mitochondrial number and caused mitochondrial dysfunction. Rbko cells had reduced oxygen consumption rate, reduced reserve capacity, an accumulation of depolarized mitochondria and displayed an altered flux of Carbon through the TCA cycle that was evident both in vivo and in vitro. These defects impair cell proliferation under conditions of mitochondria stress. Collectively, these results suggest that the most consistent changes in the proteome of Rbko tissues may not stem from changes in the levels of cell proliferation proteins, but from changes in mitochondrial function. Analysis of transcripts that are induced in Rbko tissues without a corresponding change in pro...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: E2F Family Functions: Alterations and Consequences: Oral Presentations - Invited Abstracts Source Type: research