PIP4K2B
PIP4K2B encodes PI5P4Kβ, a type II phosphatidylinositol phosphate kinase that phosphorylates PtdIns5P to produce PtdIns(4,5)P2[1]. Mechanistically, PIP4K2B links phosphoinositide metabolism to nuclear regulation because it shows prominent nuclear localization among mammalian PIP4K isoforms[2]. In mechanobiology models, PIP4K2B responds to substrate stiffness, and its depletion reduces UHRF1, nuclear envelope tension, chromatin compaction, YAP nuclear activity, and cell motility[2]. Compared with related isoforms, the β isoform has a defined nuclear-targeting mechanism, and PIP4Kβ interacts with and modulates nuclear localization of the high-activity PIP4Kα isoform[3][4]. In breast cancer, low PIP4K2B expression correlates with reduced patient survival and altered E-cadherin expression, supporting its use in tumor biology models[5]. For experimental applications, non-isoform-specific PI5P4Kα/β inhibitors disrupt cell energy metabolism, activate AMPK, inhibit mTORC1, and selectively kill p53-null tumor cells[6].
References:
- [1]. Rameh LE, et al. A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate. Nature. 1997 Nov 13;390(6656):192-6. [Content Brief]
- [2]. Poli A, et al. PIP4K2B is mechanoresponsive and controls heterochromatin-driven nuclear softening through UHRF1. Nat Commun. 2023 Mar 14;14(1):1432. [Content Brief]
- [3]. Ciruela A, et al. Nuclear targeting of the beta isoform of type II phosphatidylinositol phosphate kinase (phosphatidylinositol 5-phosphate 4-kinase) by its alpha-helix 7. Biochem J. 2000 Mar 15;346 Pt 3(Pt 3):587-91. [Content Brief]
- [4]. Bultsma Y, et al. PIP4Kbeta interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kalpha. Biochem J. 2010 Sep 1;430(2):223-35. [Content Brief]
- [5]. Keune WJ, et al. Low PIP4K2B expression in human breast tumors correlates with reduced patient survival: A role for PIP4K2B in the regulation of E-cadherin expression. Cancer Res. 2013 Dec 1;73(23):6913-25. [Content Brief]
- [6]. Chen S, et al. Pharmacological inhibition of PI5P4Kα/β disrupts cell energy metabolism and selectively kills p53-null tumor cells. Proc Natl Acad Sci U S A. 2021 May 25;118(21):e2002486118. [Content Brief]
