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Inositol pyrophosphates modulate S phase progression after pheromone-induced arrest in Saccharomyces cerevisiae (CROSBI ID 198856)

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Banfić, Hrvoje ; Bedalov, Antonio ; York, John D ; Višnjić, Dora Inositol pyrophosphates modulate S phase progression after pheromone-induced arrest in Saccharomyces cerevisiae // The Journal of biological chemistry, 288 (2013), 1717-1725. doi: 10.1074/jbc.M112.412288

Podaci o odgovornosti

Banfić, Hrvoje ; Bedalov, Antonio ; York, John D ; Višnjić, Dora

engleski

Inositol pyrophosphates modulate S phase progression after pheromone-induced arrest in Saccharomyces cerevisiae

Several studies demonstrate the activation of phosphoinositide-specific phospholipase C (PI-PLC) in nuclei of mammalian cells during synchronous progression through the cell cycle, but the downstream targets of PLC-generated inositol (1, 4, 5)-trisphospate are poorly described. The budding yeast Saccharomyces cerevisiae share similarities with endonuclear phospholipid signaling, and many recent studies pointed to the role of inositol phosphates including InsP5, InsP6, and inositol pyrophosphates PP-InsP4 and PP-InsP5 in mediating action of PLC. In this study, we investigated the changes in inositol phosphate levels in a model of a- factor-treated S. cerevisiae that allows cells to progress synchronously through the cell cycle after release from the G1 block. The results show an increase in the activity of PLC early after release from the block with a concomitant increase in the level of PPInsP5 and [PP]2-InsP4. Treatment of cells with a PLC inhibitor U73122 prevented increases in inositol phosphate levels, and blocked progression of the cells through S phase after pheromone arrest. The enzymatic activity of TAP-Kcs1 in vitro and HPLC analysis of [3H]-inositol labeled kcs1D cells confirmed that Kcs1 is the principal kinase responsible for generation of pyrophosphates in synchronously progressing cells. The analysis of plc1D, kcs1D and ddp1D yeast mutants further confirmed the role that PLC1- and Kcs1- mediated increase in pyrophosphates may have in progression through S phase. Our data provide genetic, metabolic and biochemical evidence that synthesis of inositol pyrophosphates through activation of PLC and Kcs1 play an important role in the signalling response required for cell cycle progression after mating pheromone arrest

inositol pyrophosphates; PLC1; Kcs1; cell cycle

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Podaci o izdanju

288

2013.

1717-1725

objavljeno

0021-9258

10.1074/jbc.M112.412288

Povezanost rada

Temeljne medicinske znanosti

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