Sáenz Robles, MT and Case, A and Chong, JL and Leone, G and Pipas, JM
(2011)
The retinoblastoma tumor suppressor regulates a xenobiotic detoxification pathway.
PLoS ONE, 6 (10).
Abstract
The retinoblastoma tumor suppressor (pRb) regulates cell cycle entry, progression and exit by controlling the activity of the E2F-family of transcription factors. During cell cycle exit pRb acts as a transcriptional repressor by associating with E2F proteins and thereby inhibiting their ability to stimulate the expression of genes required for S phase. Indeed, many tumors harbor mutations in the RB gene and the pRb-E2F pathway is compromised in nearly all types of cancers. In this report we show that both pRb and its interacting partners, the transcriptional factors E2F1-2-3, act as positive modulators of detoxification pathways important for metabolizing and clearing xenobiotics-such as toxins and drugs-from the body. Using a combination of conventional molecular biology techniques and microarray analysis of specific cell populations, we have analyzed the detoxification pathway in murine samples in the presence or absence of pRb and/or E2F1-2-3. In this report, we show that both pRb and E2F1-2-3 act as positive modulators of detoxification pathways in mice, challenging the conventional view of E2F1-2-3 as transcriptional repressors negatively regulated by pRb. These results suggest that mutations altering the pRb-E2F axis may have consequences beyond loss of cell cycle control by altering the ability of tissues to remove toxins and to properly metabolize anticancer drugs, and might help to understand the formation and progression rates of different types of cancer, as well as to better design appropriate therapies based on the particular genetic composition of the tumors. © 2011 Saenz Robles et al.
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Details
| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Sáenz Robles, MT | | | | | Case, A | | | | | Chong, JL | | | | | Leone, G | | | | | Pipas, JM | pipas@pitt.edu | PIPAS | |
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| Contributors: |
| Contribution | Contributors Name | Email | Pitt Username | ORCID |
|---|
| Editor | Veitia, Reiner Albert | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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| Date: |
12 October 2011 |
| Date Type: |
Publication |
| Journal or Publication Title: |
PLoS ONE |
| Volume: |
6 |
| Number: |
10 |
| DOI or Unique Handle: |
10.1371/journal.pone.0026019 |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Biological Sciences |
| Refereed: |
Yes |
| MeSH Headings: |
Animals; Animals, Newborn; Down-Regulation--genetics; E2F Transcription Factors--deficiency; E2F Transcription Factors--metabolism; Liver--metabolism; Metabolic Detoxication, Drug--genetics; Metabolic Networks and Pathways--genetics; Mice; Mice, Knockout; RNA, Messenger--genetics; RNA, Messenger--metabolism; Retinoblastoma Protein--deficiency; Retinoblastoma Protein--metabolism; Transcription, Genetic; Xenobiotics--metabolism |
| Other ID: |
NLM PMC3192141 |
| PubMed Central ID: |
PMC3192141 |
| PubMed ID: |
22022495 |
| Date Deposited: |
10 Sep 2012 14:11 |
| Last Modified: |
31 Jul 2020 17:57 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/13983 |
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