Mammalian Sterile20-like kinase 1 and the regulation of apoptosis

Souza, Patrícia Mendes de; Lindsay, Mark A.

doi:10.1042/bst0320485

Cited by 53 publications

(54 citation statements)

References 40 publications

(96 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mst1 has been reported, in response to a wide variety of apoptotic stimuli, to be a prominent stimulator during apoptosis [27], playing an important role as a caspase effector that contributes to apoptosis. Mst1 has also been shown to act upstream of MAPK kinase kinase (MAPKKK) that regulates p38 and JNK activities, acting as a putative MAPK kinase kinase kinase (MAPKKKK) [19], thus, functioning in a positive feedback pathway that amplifies the apoptotic response through MAPK activation. However, the biological significance of MAPK activation has been emphasized for only its apoptotic effects, in spite of being known to have anti-apoptotic effects as well.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation of the MAPK superfamily

Song

2008

Cellular Signalling

View full text Add to dashboard Cite

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis through caspase activation in a number of cancer cell lines while displaying minimal or no toxicity on normal cells, suggesting that this protein may hold potential for development as a new cancer therapeutic agent. Moreover, TRAIL can activate mitogen-activated protein kinases (MAPKs) in addition to caspases. However, it has not been clearly understood how MAPKs are activated by TRAIL and the biological significance of their activation.Here we show that TRAIL-induced MAPKs activation is dependent on caspase activation and that mammalian sterile 20-like kinase 1 (Mst1) functions as a mediator between caspase activation and MAPKs activation. Activation of MAPKs (JNK, p38, ERK) is differentially regulated by cleavage size (40 kDa and 36 kDa) of Mst1, which is controlled by caspase-7 and -3.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Mst1 (mammalian sterile 20-like kinase 1) is a ubiquitously expressed serine/threonine kinase having a molecular weight of 59 kD [19]. It is a mammalian homolog of the budding yeast Ste20 kinase [20].…”

Section: Introductionmentioning

confidence: 99%

Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation of the MAPK superfamily

Song

2008

Cellular Signalling

View full text Add to dashboard Cite

show abstract

“…MST1 and MST2 are mammalian sterile20-like kinases and are supposed to be involved in the induction of apoptosis (de Souza and Lindsay, 2004). TTK is known to function in the spindle checkpoint.…”

Section: Discussionmentioning

confidence: 99%

TTK/Mps1 controls nuclear targeting of c-Abl by 14-3-3-coupled phosphorylation in response to oxidative stress

et al. 2008

View full text Add to dashboard Cite

Upon exposure to genotoxic stress, the c-Abl tyrosine kinase is released from cytoplasmic 14-3-3 proteins and then is targeted to the nucleus. Phosphorylation of Thr735 in c-Abl is critical for binding to 14-3-3; however, kinases responsible for this phosphorylation are unknown. Here, we identify CLK1, CLK4, MST1, MST2 and TTK (also known as Mps1) as novel Thr735 kinases in vitro by expression cloning strategy using phosphospecific antibody. We also demonstrate that ectopic expression of these kinases is capable for phosphorylation of Thr735 in cells. Importantly, upon exposure to oxidative stress, phosphorylation of Thr735 is transiently upregulated, and the status of this phosphorylation remains unchanged in cells silenced for CLK1, CLK4, MST1 or MST2. By contrast, knockdown of TTK attenuates phosphorylation of Thr735, suggesting that TTK is a physiological kinase that phosphorylates Thr735. In concert with these results, we show that, in cells silenced for TTK, c-Abl is accumulated in the nucleus even in unstressed condition and no further targeting into the nucleus occurs after oxidative stress. Moreover, nuclear entrapment of c-Abl by knocking down TTK enhances oxidative stress-induced apoptosis. These findings provide evidence that TTK phosphorylates c-Abl at Thr735 and that this phosphorylation is of importance to the cytoplasmic sequestration of c-Abl.

show abstract

“…Protein kinases generally have key roles in signal transduction driven by various stimuli (Karin and Hunter, 1995). For example, mammalian Ste20-like kinase-1 (MST1) is a Ser/Thr kinase that is activated by apoptosis-inducing stimuli (de Souza and Lindsay, 2004). 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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

View full text Add to dashboard Cite

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.

show abstract

Mammalian Sterile20-like kinase 1 and the regulation of apoptosis

Cited by 53 publications

References 40 publications

Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation of the MAPK superfamily

Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation of the MAPK superfamily

TTK/Mps1 controls nuclear targeting of c-Abl by 14-3-3-coupled phosphorylation in response to oxidative stress

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

Contact Info

Product

Resources

About