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Mornings with art, lessons learned: Feedback regulation, restriction threshold biology, and redundancy govern molecular stress responses
Author(s) -
Bey Erik A.,
WuerzbergerDavis Shelly M.,
Pink John J.,
Yang ChinRang,
Araki Shinako,
Reinicke Kathryn E.,
Bentle Melissa S.,
Dong Ying,
Cataldo Eva,
Criswell Tracy L.,
Wagner Mark W.,
Li Longshan,
Gao Jinming,
Boothman David A.
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20783
Subject(s) - redundancy (engineering) , biology , stress (linguistics) , computational biology , evolutionary biology , engineering , reliability engineering , linguistics , philosophy
Work from the laboratory of Dr. Arthur B. Pardee has highlighted basic principles that govern cellular and molecular biological processes in living cells. Among the most important governing principles in cellular and molecular responses are: (i) threshold “restriction” responses, wherein a level of response is reached and a “point of no return” is achieved; (ii) feedback regulation; and (iii) redundancy. Lessons learned from the molecular biology of cellular stress responses in mammalian cancer versus normal cells after ionizing radiation (IR) or chemotherapeutic agent exposures reveal similar instances of these guiding principles in mammalian cells. Among these are the: (i) induction of cell death responses by β‐lapachone (β‐lap), a naphthoquinone anti‐tumor agent that kills cancer cells via an NQO1 (i.e., X‐ray‐inducible protein‐3, xip3)‐dependent mechanism; (ii) induction of secretory clusterin (sCLU) in response to TGF‐β1 exposure, and the ability of induced sCLU protein to down‐regulate TGF‐β1 signaling; and (iii) induction of DNA mismatch repair‐dependent G 2 cell cycle checkpoint responses after exposure to alkylating agents. We have learned these lessons and now adopted strategies to exploit them for improved therapy. These examples will be discussed and compared to the pioneering findings of researchers in the Pardee laboratory over the years. J. Cell. Physiol. 209: 604–610, 2006. © 2006 Wiley‐Liss, Inc.