p110α activity at the M-to-G1 transition is critical for cellular proliferation and reentry into the cell cycle
p110α activity at the M-to-G1 transition is critical for cellular proliferation and reentry into the cell cycle
Phosphoinositide 3-kinase (PI3K) signaling pathway is essential for normal physiology and is impaired in diseases such as premalignant hyperproliferative disorders, primary immunodeficiency, metabolic disorders, and cancer. Although the core PI3K pathway components are known today, a long-standing gap in our knowledge of PI3K signaling concerns how distinct PI3K isoforms and their activity patterns contribute to the functional consequences of pathway upregulation. In order to address this issue, we devised a molecular genetic cell model, which allowed temporal regulation of the indispensable PI3K isoform, p110α in distinct stages of the cell cycle. We found that late M and early G1 presence of p110α is key for proper cell cycle progression, whereas its S-phase abundance was redundant. Our results also emphasize a critical dependence of cell cycle reentry on early G1 activity of p110α. Collectively, our findings provide a temporal perspective to p110α activation and offer insight into which wave of PI3K activity could be essential for cell cycle progression.
___
- Alvarez B, Martínez AC, Burgering BMT, Carrera AC (2001). Forkhead transcription factors contribute to execution of the mitotic programme in mammals. Nature 413: 744–747. doi: 10.1038/35099574
- Alvarez B, Garrido E, Garcia-Sanz JA, Carrera AC (2003). Phosphoinositide 3-kinase activation regulates cell division time by coordinated control of cell mass and cell cycle progression rate. Journal of Biological Chemistry 278: 26466– 26473. doi: 10.1074/jbc.M300663200
- Cizmecioglu O, Ni J, Xie S, Zhao JJ, Roberts TM (2016). Rac1- mediated membrane raft localization of PI3K/p110β is required for its activation by GPCRs or PTEN loss. eLife 5. doi: 10.7554/elife.17635
- Cizmecioglu O, Krause A, Bahtz R, Ehret L, Malek N et al. (2012). Plk2 regulates centriole duplication through phosphorylationmediated degradation of Fbxw7 (human Cdc4). Journal of Cell Science 125: 981–992. doi: 10.1242/jcs.095075
- Guerrero-Zotano A, Mayer IA, Arteaga CL (2016). PI3K/AKT/ mTOR: role in breast cancer progression, drug resistance, and treatment. Cancer and Metastasis Reviews 35: 515–524. doi: 10.1007/s10555-016-9637-x
- Guertin DA, Sabatini DM (2007). Defining the Role of mTOR in Cancer. Cancer Cell 12: 9–22. doi: 10.1016/j.ccr.2007.05.008
- Jia S, Roberts TM, Zhao JJ (2009). Should individual PI3 kinase isoforms be targeted in cancer? Current Opinion in Cell Biology 21: 199–208. doi: 10.1016/j.ceb.2008.12.007
- Jones SM, Kazlauskas A (2001). Growth-factor-dependent mitogenesis requires two distinct phases of signalling. Nature Cell Biology 3: 165–172. doi: 10.1038/35055073
- Kumar A, Redondo-Muñoz J, Perez-García V, Cortes I, Chagoyen M et al. (2011). Nuclear but Not Cytosolic Phosphoinositide 3-Kinase Beta Has an Essential Function in Cell Survival. Molecular and Cellular Biology 31: 2122. doi: 10.1128/ MCB.01313-10
- Laoukili J, Kooistra MRH, Brás A, Kauw J, Kerkhoven RM et al. (2005). FoxM1 is required for execution of the mitotic programme and chromosome stability. Nature Cell Biology 7: 126–136. doi: 10.1038/ncb1217
- Liang J, Slingerland JM (2003). Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression. Cell cycle (Georgetown, Tex.) 2: 336–342. doi: 10.4161/cc.2.4.433
- Liu P, Cheng H, Roberts TM, Zhao JJ (2009). Targeting the phosphoinositide 3-kinase pathway in cancer. Nature Reviews Drug Discovery 8: 627–644. doi: 10.1038/nrd2926
- Lundberg AS, Weinberg RA (1998). Functional Inactivation of the Retinoblastoma Protein Requires Sequential Modification by at Least Two Distinct Cyclin-cdk Complexes. Molecular and Cellular Biology 18: 753–761. doi: 10.1128/mcb.18.2.753
- Manning BD, Cantley LC (2007). AKT/PKB Signaling: Navigating Downstream. Cell 129: 1261–1274. doi: 10.1016/j. cell.2007.06.009
- Mayer IA, Arteaga CL (2016). The PI3K/AKT pathway as a target for cancer treatment. Annual Review of Medicine 67: 11–28. doi: 10.1146/annurev-med-062913-051343
- Naetar N, Soundarapandian V, Litovchick L, Goguen KL, Sablina AA et al. (2014). PP2A-mediated regulation of ras signaling in G2 is essential for stable quiescence and normal G1 length. Molecular Cell 54 (6): 932-45. doi: 10.1016/j.molcel.2014.04.023
- Narayan P, Prowell TM, Gao JJ, Fernandes LL, Li E et al. (2021). FDA approval summary: Alpelisib plus fulvestrant for patients with hr-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer. Clinical Cancer Research 27: 1842– 1849. doi: 10.1158/1078-0432.CCR-20-3652
- Pyronnet S, Dostie J, Sonenberg N (2001). Suppression of capdependent translation in mitosis. Genes and Development 15: 2083–2093. doi: 10.1101/gad.889201
- Sakaue-Sawano A, Kurokawa H, Morimura T, Hanyu A, Hama H et al. (2008). Visualizing Spatiotemporal Dynamics of Multicellular Cell-Cycle Progression. Cell 132: 487–498. doi: 10.1016/j.cell.2007.12.033
- Shtivelman E, Sussman J, Stokoe D (2002). A role for PI 3-kinase and PKB activity in the G2/M phase of the cell cycle. Current Biology 12: 919–924. doi: 10.1016/S0960-9822(02)00843-6
- van Weeren PC, de Bruyn KMT, de Vries-Smits AMM, van Lint J, Burgering BMT (1998). Essential role for protein kinase B (PKB) in insulin-induced glycogen synthase kinase 3 inactivation. Characterization of dominant-negative mutant of PKB. Journal of Biological Chemistry 273: 13150–13156. doi: 10.1074/jbc.273.21.13150
- Wymann MP, Pirola L (1998). Structure and function of phosphoinositide 3-kinases. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids 1436: 127–150. doi: 10.1016/S0005-2760(98)00139-8
- ISSN: 1300-0152
- Yayın Aralığı: Yılda 6 Sayı
- Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler
Chuan FU, Xiating LI, Lichun SUN, Tianlun FAN
siRNA-mediated stathmin1 silencing inhibits proliferation of prostate carcinoma cell line
Ebru ETEM ÖNALAN, Selcen GÖKTÜRK, Gökhan ARTAŞ, Asude AKSOY, Mustafa KOÇ, Ahmet TEKTEMUR, Asuman VAROĞLU
Point-of-care diagnosis of cervical cancer: potential protein biomarkers in cervicovaginal fluid
Özgüç TAKMAZ, Mete GÜNGÖR, Ahmet Tarık BAYKAL, Büşra KÖSE
Design and in vitro, in vivo evaluation of antioxidant bioadhesive gels for burn treatment
Çetin PEKÇETİN, Evren ALGIN YAPAR, Göksel GÖKÇE, Alper BAĞRIYANIK, Sinem Yaprak KARAVANA, Gülşen AYBAR TURAL, Evren Homan GÖKÇE
Cytoplasmically localized tRNA-derived fragments inhibit translation in Drosophila S2 cells