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The retinoblastoma tumor suppressor regulates a xenobiotic detoxification pathway

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).

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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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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Sáenz Robles, MT
Case, A
Chong, JL
Leone, G
Pipas, JMpipas@pitt.eduPIPAS
ContributionContributors NameEmailPitt UsernameORCID
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


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