- Author
-
W.J.H. Keune
- Title
- Phosphoinositides and lipid kinases in oxidative stress signalling and cancer
- Supervisors
- Co-supervisors
-
N. Divecha
- Award date
- 21 November 2013
- Number of pages
- 189
- ISBN
- 9789461823458
- Document type
- PhD thesis
- Faculty
- Faculty of Science (FNWI)
- Institute
- Swammerdam Institute for Life Sciences (SILS)
- Abstract
-
Phosphoinositides are implicated in virtually all aspects of cellular welfare. They help to maintain the structure of biomembranes, but are also essential signal transduction molecules. This is illustrated by PtdIns(4,5)P2, a versatile and important phosphoinositide that regulates many cellular processes including cell survival, calcium homeostasis, vesicular trafficking, cytokinesis, stress responses and cell adhesion. Cells use various enzymes to regulate PtdIns(4,5)P2 levels, including lipid kinases, lipid phosphatases and lipases. PtdIns(4,5)P2 can be synthesized by two closely related families of lipid kinases. Phosphatidylinositol-4-phosphate (PtdIns4P) 5-kinase (PIP5K) phosphorylates PtdIns4P and phosphatidylinositol-5-phosphate (PtdIns5P) 4-kinase (PIP4K) phosphorylates PtdIns5P to make PtdIns(4,5)P2. Cellular PtdIns4P is approximately ten times more abundant than PtdIns5P and therefore PtdIns(4,5)P2 is likely generated by PIP5K mainly. In vivo studies in animals and in mammalian cells suggest that PIP4Ks primarily regulate the level of PtdIns5P, although they may also regulate a specific pool of PtdIns(4,5)P2. PtdIns5P is the latest addition to the ‘palet’ of phosphoinositides and it is the least understood one.
In this thesis, I have examined biochemical and functional aspects of PtdIns5P and the PIP4Ks that determine its levels in the cell. I have investigated how PtdIns5P levels change in response to redox signaling, or in response to the activity of the isoforms PIP4K2A and PIP4K2B and I have evaluated PIP4K2B expression in breast tumours. - Note
- Research conducted at: Universiteit van Amsterdam
- Persistent Identifier
- https://hdl.handle.net/11245/1.399675
- Downloads
-
Thesis
Cover
Title pages
Table of contents
Chapter 1: General introduction
Chapter 2: PtdIns5P and Pin1 in oxidative stress signaling
Chapter 3: Regulation of phosphatidylinositol-5-phosphate signaling by Pin1 determines sensitivity to oxidative stress
Chapter 4: Pin1 associates with phosphoinositides and overexpression of PIP5K inhibits Pin1 mediated transcriptional activity of CDKN1B and CCND1
Chapter 5: Phosphoinositide signalling in the nucleus
Chapter 6: PIP4Kβ interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kα
Chapter 7: Low PIP4K2B expression in human breast tumours correlates with reduced patient survival: A role for PIP4K2B in the regulation of E-cadherin expression
Chapter 8: General discussion
Summary
Nederlandse samenvatting
List of publications
List of abbreviations
Dankwoord
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