Abstract/Details

Regulation of apoptosis by p53 and the ecdysone receptor co-activator TRR in Drosophila


2008 2008

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Abstract (summary)

The tumor suppressor protein p53 is a known regulator of apoptosis following exposure to DNA damage-inducing radiation. This function is conserved in Drosophila, where p53 can induce apoptosis through up-regulation of the cell death gene reaper (rpr). The Drosophila Ecdysone receptor (ER), a receptor for the steroid hormone ecdysone, is known to regulate programmed cell death during development, also through induction of rpr. While there is much data showing that p53 activity can be influenced by steroid hormone receptors, the precise nature of any functional interaction between the two is unclear. This work shows that ER is required for induction of apoptosis in embryos following exposure to radiation. Together with p53, the ER and its co-activator methyltransferase (MTase) Trithorax-related (TRR) are essential for the strong increase in transcription of rpr and two other cell death genes, sickle and grim, showing a direct role for the steroid hormone response in this apoptotic pathway. Mechanistically, ER influences p53 function through direct methylation of p53 by its co-activator TRR. This occurs on the rpr gene, where TRR can specifically di-methylate p53 at lysine 379 after radiation treatment, and this modification is essential in vivo for induction of apoptosis. Thus, these results demonstrate a specific mechanism by which a steroid hormone receptor and p53 are involved in co-regulation of cell death following DNA damage-induced apoptosis. This new mechanism may be applicable to the previously described relationship between p53 and the estrogen receptor during cancer treatment, as the human TRR homolog (ALR) is part of an estrogen receptor co-regulator complex.

Indexing (details)


Subject
Genetics
Classification
0369: Genetics
Identifier / keyword
Biological sciences; Apoptosis; Ecdysone receptor; Methylation; Radiation
Title
Regulation of apoptosis by p53 and the ecdysone receptor co-activator TRR in Drosophila
Author
Riley, Kristen Marie
Number of pages
112
Publication year
2008
Degree date
2008
School code
0272
Source
DAI-B 71/07, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781124101651
University/institution
Thomas Jefferson University
University location
United States -- Pennsylvania
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3415855
ProQuest document ID
741148886
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/741148886
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