Author
Wei Gu
Other affiliations: Rockefeller University, Columbia University Medical Center
Bio: Wei Gu is an academic researcher from Columbia University. The author has contributed to research in topics: Acetylation & Ubiquitin ligase. The author has an hindex of 82, co-authored 177 publications receiving 34525 citations. Previous affiliations of Wei Gu include Rockefeller University & Columbia University Medical Center.
Topics: Acetylation, Ubiquitin ligase, DNA damage, Medicine, Mdm2
Papers published on a yearly basis
Papers
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TL;DR: It is demonstrated that p53 can be modified by acetylated both in vivo and in vitro, indicating a novel pathway for p53 activation and providing an example of an acetylation-mediated change in the function of a nonhistone regulatory protein.
2,583 citations
TL;DR: It is shown that mammalian Sir2alpha physically interacts with p53 and attenuates p53-mediated functions, and Nicotinamide inhibits an NAD-dependent p53 deacetylation induced by Sir2 alpha, and also enhances the p53 acetylation levels in vivo.
2,021 citations
TL;DR: It is shown that p53 inhibits cystine uptake and sensitizes cells to ferroptosis, a non-apoptotic form of cell death, by repressing expression of SLC7A11, a key component of the Cystine/glutamate antiporter.
Abstract: Although p53-mediated cell-cycle arrest, senescence and apoptosis serve as critical barriers to cancer development, emerging evidence suggests that the metabolic activities of p53 are also important. Here we show that p53 inhibits cystine uptake and sensitizes cells to ferroptosis, a non-apoptotic form of cell death, by repressing expression of SLC7A11, a key component of the cystine/glutamate antiporter. Notably, p53(3KR), an acetylation-defective mutant that fails to induce cell-cycle arrest, senescence and apoptosis, fully retains the ability to regulate SLC7A11 expression and induce ferroptosis upon reactive oxygen species (ROS)-induced stress. Analysis of mutant mice shows that these non-canonical p53 activities contribute to embryonic development and the lethality associated with loss of Mdm2. Moreover, SLC7A11 is highly expressed in human tumours, and its overexpression inhibits ROS-induced ferroptosis and abrogates p53(3KR)-mediated tumour growth suppression in xenograft models. Our findings uncover a new mode of tumour suppression based on p53 regulation of cystine metabolism, ROS responses and ferroptosis.
1,677 citations
TL;DR: It is proposed that antirepression, the release of p53 from repression by factors such as Mdm2 and MdmX, is a key step in the physiological activation of p 53.
1,503 citations
TL;DR: It is shown that the mammalian SIR2 ortholog SIRT1 deacetylates and represses the activity of the forkhead transcription factor Foxo3a and other mammalian forkhead factors, and how down-regulating these two classes of damage-responsive mammalian factors may favor long lifespan under certain environmental conditions, such as calorie restriction is speculated.
1,363 citations
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TL;DR: Nine tentative hallmarks that represent common denominators of aging in different organisms are enumerated, with special emphasis on mammalian aging, to identify pharmaceutical targets to improve human health during aging, with minimal side effects.
9,980 citations
TL;DR: It is argued that redox biology, rather than oxidative stress, underlies physiological and pathological conditions.
4,297 citations
TL;DR: Recent advances in understanding how epigenetic alterations participate in the earliest stages of neoplasia, including stem/precursor cell contributions, are reviewed and the growing implications of these advances for strategies to control cancer are discussed.
4,269 citations
TL;DR: The Janus kinases and signal transducers and activators of transcription, and many of the interferon-induced proteins, play important alternative roles in cells, raising interesting questions as to how the responses to the interFERons intersect with more general aspects of cellular physiology and how the specificity of cytokine responses is maintained.
Abstract: Interferons play key roles in mediating antiviral and antigrowth responses and in modulating immune response. The main signaling pathways are rapid and direct. They involve tyrosine phosphorylation and activation of signal transducers and activators of transcription factors by Janus tyrosine kinases at the cell membrane, followed by release of signal transducers and activators of transcription and their migration to the nucleus, where they induce the expression of the many gene products that determine the responses. Ancillary pathways are also activated by the interferons, but their effects on cell physiology are less clear. The Janus kinases and signal transducers and activators of transcription, and many of the interferon-induced proteins, play important alternative roles in cells, raising interesting questions as to how the responses to the interferons intersect with more general aspects of cellular physiology and how the specificity of cytokine responses is maintained.
4,026 citations
TL;DR: The evidence is reviewed that both supports and conflicts with the free radical theory of aging and the growing link between mitochondrial metabolism, oxidant formation, and the biology of aging is examined.
3,870 citations