Research Perspectives:

Insights into 4E-BP1 and p53 mediated regulation of accelerated cell senescence

Suzan K. Chao, Susan Band Horwitz _ and Hayley M. McDaid

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Oncotarget. 2011; 2:89-98. https://doi.org/10.18632/oncotarget.221

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Suzan K. Chao1, Susan Band Horwitz1, and Hayley M. McDaid1,2

1Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461

2Department of Medicine (Oncology) Albert Einstein College of Medicine, Bronx, NY 10461

Keywords: Senescence, 4E-BP1, mTORC1, p53, discodermolide

Received: February 22, 2011; Accepted: February 22, 2011; Published: February 22, 2011;


Susan Band Horwitz, e-mail:

Hayley McDaid, e-mail:


Senescence is a valid tumor suppressive mechanism in cancer. Accelerated cell senescence describes the growth arrested state of cells that have been treated with anti-tumor drugs, such as doxorubicin that induce a DNA damage response. Discodermolide, a microtubule-stabilizing agent, is a potent inducer of accelerated cell senescence. Resistance to discodermolide is mediated via resistance to accelerated cell senescence, and is associated with reduced expression of the mTORC1 substrate, 4E-BP1 and increased expression of p53 [1]. Although the association of p53 with senescence induction is well-characterized, senescence reversion in the presence of high expression of p53 has not been well-documented. Furthermore, studies addressing the role of mTOR signaling in regulating senescence have been limited and recent data implicate a novel, senescence-associated role for 4E-BP1 in crosstalk with the transcription factor p53. This research perspective will address these somewhat contradictory findings and summarize recent research regarding senescence and mTORC1 signaling.

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