Self-regulatory role of 4-hydroxynonenal in signaling for stress-induced programmed cell death.
Within the last two decades, 4-hydroxynonenal has emerged as an important second messenger involved in the regulation of various cellular processes. Our recent studies suggest that HNE can induce apoptosis in various cells through the death receptor Fas (CD95)-mediated extrinsic pathway as well as through the p53-dependent intrinsic pathway. Interestingly, through its interaction with the nuclear protein Daxx, HNE can self-limit its apoptotic role by translocating Daxx to cytoplasm where it binds to Fas and inhibits Fas-mediated apoptosis. In this paper, after briefly describing recent studies on various biological activities of HNE, based on its interactions with Fas, Daxx, and p53, we speculate on possible mechanisms through which HNE may affect a multitude of cellular processes and draw a parallel between signaling roles of H(2)O(2) and HNE.
Awasthi
Yogesh C
YC
Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA. yawasthi@hsc.unt.edu
Sharma
Rajendra
R
Sharma
Abha
A
Yadav
Sushma
S
Singhal
Sharad S
SS
Chaudhary
Pankaj
P
Awasthi
Sanjay
S
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D056970:Co-Repressor Proteins; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000447:Aldehydes; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D016877:Oxidants; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D006861:Hydrogen Peroxide; C027576:4-hydroxy-2-nonenal