p300-CBP Transcription Factors

Publication Title: 
Nature Chemical Biology

Cellular damage invoked by reactive oxygen species plays a key role in the pathobiology of cancer and aging. Forkhead box class O (FoxO) transcription factors are involved in various cellular processes including cell cycle regulation, apoptosis and resistance to reactive oxygen species, and studies in animal models have shown that these transcription factors are of vital importance in tumor suppression, stem cell maintenance and lifespan extension.

Author(s): 
Dansen, Tobias B.
Smits, Lydia M. M.
van Triest, Miranda H.
de Keizer, Peter L. J.
van Leenen, Dik
Koerkamp, Marian Groot
Szypowska, Anna
Meppelink, Amanda
Brenkman, Arjan B.
Yodoi, Junji
Holstege, Frank C. P.
Burgering, Boudewijn M. T.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Forkhead box class O 3a (FOXO3a) is a transcription factor and tumor suppressor linked to longevity that determines cell fate through activating transcription of cell differentiation, survival, and apoptotic genes. Recruitment of the coactivator CBP/p300 is a crucial step in transcription, and we revealed that in addition to conserved region 3 (CR3) of FOXO3a, the C-terminal segment of CR2 (CR2C) binds CBP/p300 and contributes to transcriptional activity.

Author(s): 
Wang, Feng
Marshall, Christopher B.
Yamamoto, Kazuo
Li, Guang-Yao
Gasmi-Seabrook, GeneviËve M. C.
Okada, Hitoshi
Mak, Tak W.
Ikura, Mitsuhiko
Publication Title: 
Molecular Cell

Cellular processes function through multistep pathways that are reliant on the controlled association and disassociation of sequential protein complexes. While dynamic action is critical to propagate and terminate work, the mechanisms used to disassemble biological structures are not fully understood. Here we show that the p23 molecular chaperone initiates disassembly of protein-DNA complexes and that the GCN5 acetyltransferase prolongs the dissociated state through lysine acetylation.

Author(s): 
Zelin, Elena
Zhang, Yang
Toogun, Oyetunji A.
Zhong, Sheng
Freeman, Brian C.
Publication Title: 
Molecular and Cellular Endocrinology

We have shown that melatonin induces histone hyperacetylation in vitro and in vivo. To clarify the mechanisms involved, we have now investigated its effects on histone acetylation and signaling pathways in human SH-SY5Y neuroblastoma cells, which express melatonin MT1 receptors. Melatonin caused significant concentration-dependent increases in both histone H3 and H4 acetylation. Blockade of melatonin receptors with luzindole abolished the histone hyperacetylating effect of melatonin, whereas inhibition of MAPK-ERK by PD98059 attenuated but did not block this effect.

Author(s): 
Pan, Yi
Niles, Lennard P.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Transcriptional control of metabolic circuits requires coordination between specific transcription factors and coregulators and is often deregulated in metabolic diseases. We characterized here the mechanisms through which the coactivator SRC-3 controls energy homeostasis. SRC-3 knock-out mice present a more favorable metabolic profile relative to their wild-type littermates. This metabolic improvement in SRC-3(-/-) mice is caused by an increase in mitochondrial function and in energy expenditure as a consequence of activation of PGC-1alpha.

Author(s): 
Coste, Agnès
Louet, Jean-Francois
Lagouge, Marie
Lerin, Carles
Antal, Maria Cristina
Meziane, Hamid
Schoonjans, Kristina
Puigserver, Pere
O'Malley, Bert W.
Auwerx, Johan
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