Sterile 20 Kinase Phosphorylates Histone H2B at Serine 10 during Hydrogen Peroxide-Induced Apoptosis in S. cerevisiae

Ahn, Sung-Hee; Cheung, Wang L.; Hsu, Jer-Yuan; Diaz, Robert L.; Smith, M. Mitchell; Allis, C. David

doi:10.1016/j.cell.2004.11.016

Cited by 232 publications

(213 citation statements)

References 36 publications

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“…For Ste20, nuclear translocation has been proposed to allow it to phosphorylate histone H2B and promote apoptosis in response to oxidative stress (Ahn et al, 2005), but preliminary tests suggest that neither the BR domain nor the CRIB domain is required for this process (S.-H. Ahn and C. D. Allis, personal communication). Gic1 shows some nuclear affinity, but chimeras that lack this localization still function normally (see Figure 7D).…”

Section: Roles For Charge and Hydrophobicitymentioning

confidence: 99%

Identification of Novel Membrane-binding Domains in Multiple Yeast Cdc42 Effectors

Takahashi

Pryciak

2007

MBoC

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The Rho-type GTPase Cdc42 is a central regulator of eukaryotic cell polarity and signal transduction. In budding yeast, Cdc42 regulates polarity and mitogen-activated protein (MAP) kinase signaling in part through the PAK-family kinase Ste20. Activation of Ste20 requires a Cdc42/Rac interactive binding (CRIB) domain, which mediates its recruitment to membrane-associated Cdc42. Here, we identify a separate domain in Ste20 that interacts directly with membrane phospholipids and is critical for its function. This short region, termed the basic-rich (BR) domain, can target green fluorescent protein to the plasma membrane in vivo and binds PIP 2 -containing liposomes in vitro. Mutation of basic or hydrophobic residues in the BR domain abolishes polarized localization of Ste20 and its function in both MAP kinase-dependent and independent pathways. Thus, Cdc42 binding is required but is insufficient; instead, direct membrane binding by Ste20 is also required. Nevertheless, phospholipid specificity is not essential in vivo, because the BR domain can be replaced with several heterologous lipid-binding domains of varying lipid preferences. We also identify functionally important BR domains in two other yeast Cdc42 effectors, Gic1 and Gic2, suggesting that cooperation between protein-protein and protein-membrane interactions is a prevalent mechanism during Cdc42-regulated signaling and perhaps for other dynamic localization events at the cell cortex.

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Section: Roles For Charge and Hydrophobicitymentioning

confidence: 99%

Identification of Novel Membrane-binding Domains in Multiple Yeast Cdc42 Effectors

Takahashi

Pryciak

2007

MBoC

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“…H2A and H2B have been reported to possess acetylation (H2A: K5, K9 and H2B: K5, K12, K15, K20), phosphorylation (H2A: S1 and H2B: S10), monomethylation (H2A: K15 and H2B: K5, K43) and ubiquitination (H2A: K119 and H2B: K120/K123) [1,14,16,[36][37][38][39][40]. Thus the unambiguous assignment of the species in these profiles is complicated by possible presence of these modifications along with the variants.…”

Section: Core Histone Profilesmentioning

confidence: 99%

Liquid chromatography mass spectrometry profiling of histones

Jacob

Amunugama

et al. 2007

Journal of Chromatography B

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Here we describe the use of reverse-phase liquid chromatography mass spectrometry (RP-LC-MS) to simultaneously characterize variants and post-translationally modified isoforms for each histone. The analysis of intact proteins significantly reduces the time of sample preparation and simplifies data interpretation. LC-MS analysis and peptide mass mapping have previously been applied to identify histone proteins and to characterize their post-translational modifications. However, these studies provided limited characterization of both linker histones and core histones. The current LC-MS analysis allows for the simultaneous observation of all histone PTMs and variants (both replacement and bulk histones) without further enrichment, which will be valuable in comparative studies. Protein identities were verified by the analysis of histone H2A species using RPLC fractionation, AU-PAGE separation and nano-LC-MS/MS.

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“…Lehtinen et al (2006) reported that MST1 is activated by H 2 O 2 and induces cell death by phosphorylating the transcription factor FOXO in primary mammalian neurons. Furthermore, Ste20 mediates H 2 O 2 -induced cell death by phosphorylating histone H2B in Saccharomyces cerevisiae (Ahn et al, 2005). These studies implicate MST1 as a crucial kinase in H 2 O 2 -induced cell death, but MST1 activation mechanisms by H 2 O 2 have yet to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Oligomeric peroxiredoxin-I is an essential intermediate for p53 to activate MST1 kinase and apoptosis

et al. 2011

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Mammalian Ste20-like kinase-1 (MST1) kinase mediates H 2 O 2 -induced cell death by anticancer drugs such as cisplatin in a p53-dependent manner. However, the mechanism underlying MST1 activation by H 2 O 2 remains unknown. Here we show that peroxiredoxin-I (PRX-I) is an essential intermediate in H 2 O 2 -induced MST1 activation and cisplatin-induced cell death through p53. Cell stimulation with H 2 O 2 resulted in PRX-I oxidation to form homo-oligomers and interaction with MST1, leading to MST1 autophosphorylation and augmentation of kinase activity. In addition, RNA interference knockdown experiments indicated that endogenous PRX-I is required for H 2 O 2 -induced MST1 activation. Live-cell imaging showed H 2 O 2 generation by cisplatin treatment, which likewise caused PRX-I oligomer formation, MST1 activation and cell death. Cisplatin-induced PRX-I oligomer formation was not observed in embryonic fibroblasts obtained from p53-knockout mice, confirming the importance of p53. Indeed, ectopic expression of p53 induced PRX-I oligomer formation and cell death, both of which were cancelled by the antioxidant NAC. Moreover, we succeeded in reconstituting H 2 O 2 -induced MST1 activation in vitro, using purified PRX-I and MST1 proteins. Collectively, our results show a novel PRX-I function to cause cell death in response to high levels of oxidative stress by activating MST1, which underlies the p53-dependent cytotoxicity caused by anticancer agents.

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Sterile 20 Kinase Phosphorylates Histone H2B at Serine 10 during Hydrogen Peroxide-Induced Apoptosis in S. cerevisiae

Cited by 232 publications

References 36 publications

Identification of Novel Membrane-binding Domains in Multiple Yeast Cdc42 Effectors

Identification of Novel Membrane-binding Domains in Multiple Yeast Cdc42 Effectors

Liquid chromatography mass spectrometry profiling of histones

Oligomeric peroxiredoxin-I is an essential intermediate for p53 to activate MST1 kinase and apoptosis

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