| Title: | Inositol pyrophosphates modulate cell cycle independently of alteration in telomere length |
| Author(s): | Banfic H; Crljen V; Lukinovic-Skudar V; Dembitz V; Lalic H; Bedalov A; Visnjic D; |
| Address: | "Department of Physiology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia. Electronic address: hrvoje.banfic@zg.t-com.hr. Department of Physiology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia. Fred Hutchinson Cancer Reaserch Center, Seattle, WA 98109, USA" |
| DOI: | 10.1016/j.jbior.2015.09.003 |
| ISSN/ISBN: | 2212-4934 (Electronic) 2212-4926 (Linking) |
| Abstract: | "Synthesis of inositol pyrophosphates through activation of Kcs1 plays an important role in the signalling response required for cell cycle progression after mating pheromone arrest. Overexpression of Kcs1 doubled the level of inositol pyrophosphates when compared to wild type cells and 30 min following the release from alpha-factor block further increase in inositol pyrophosphates was observed, which resulted that cells overexpressing Kcs1 reached G2/M phase earlier than wild type cells. Similar effect was observed in ipk1Delta cells, which are unable to synthesize IP6-derived inositol pyrophosphates (IP7 and IP8) but will synthesize IP5-derived inositol pyrophosphates (PP-IP4 and (PP)2-IP3). Although ipk1Delta cells have shorter telomeres than wild type cells, overexpression of Kcs1 in both strains have similar effect on cell cycle progression. As it is known that PP-IP4 regulates telomere length through Tel1, inositol polyphosphates, cell cycle and telomere length were determined in tel1Delta cells. The release of the cells from alpha-factor block and overexpression of Kcs1 in tel1Delta cells produced similar effects on inositol pyrophosphates level and cell cycle progression when compared to wild type cells, although tel1Delta cells possesses shorter telomeres than wild type cells. It can be concluded that telomere length does not affect cell cycle progression, since cells with short telomeres (ipk1Delta and tel1Delta) progress through cell cycle in a similar manner as wild type cells and that overexpression of Kcs1 in cells with either short or normal telomeres will increase S phase progression without affecting telomere length. Furthermore, IP5-derived inositol pyrophosphates can compensate for the loss of IP6-derived inositol pyrophosphates, in modulating S phase progression of the cell cycle" |
| Keywords: | *Cell Cycle Cell Division Inositol Phosphates/*metabolism Saccharomyces cerevisiae/*cytology/genetics/metabolism Saccharomyces cerevisiae Proteins/genetics/metabolism Signal Transduction Telomere/genetics/*metabolism Cell cycle Inositol pyrophosphates Ipk; |
| Notes: | "MedlineBanfic, Hrvoje Crljen, Vladiana Lukinovic-Skudar, Vesna Dembitz, Vilma Lalic, Hrvoje Bedalov, Antonio Visnjic, Dora eng Research Support, Non-U.S. Gov't England 2015/10/09 Adv Biol Regul. 2016 Jan; 60:22-28. doi: 10.1016/j.jbior.2015.09.003. Epub 2015 Sep 26" |
