IP6K2

IP6K2 Full Name

inositol hexakisphosphate kinase 2

IP6K2 Introduction

IP6K2 is an enzyme that catalyzes the conversion of inositol hexakisphosphate (IP6) into inositol pyrophosphates such as IP7, signaling molecules involved in regulating apoptosis, metabolism, and stress responses. IP6K2 is a member of the inositol phosphate kinase family. It is widely expressed in human tissues. It is mainly located in the cytoplasm and nucleus. It has been shown to participate in transcriptional regulation and protein–protein interactions. The activity of IP6K2 converges environmental, energetic, and stress signals to allow fine regulation of cell fate.

Figure 1. Inositol polyphosphate signaling cascade.(Source: Snyder SH, 2011)

From a functional perspective, IP6K2 has been robustly linked to pro-apoptotic signaling. In this capacity, IP6K2 augments p53-dependent programmed cell death through nuclear protein interactions and modulation of p53 transcriptional activity, emerging as a potential factor in the regulation of cellular sensitivity to DNA-damaging agents. IP6K2 has also been shown to regulate mitochondrial integrity, metabolic flux and autophagy. It is also known that the inositol pyrophosphate products of IP6K2 are able to mediate ATP consumption, phosphate homeostasis and protein ubiquitination. Loss or suppression of IP6K2 promotes reduced apoptosis, altered metabolic adaptation and improved cellular survival in stress, while overexpression of IP6K2 promotes apoptosis and chemosensitization to chemotherapeutics.

Clinically, IP6K2 has been associated with tumorigenesis, tumor progression and therapy response. Reduced IP6K2 expression has been associated with apoptosis-refractory tumors and poor clinical outcome in several cancer types and may therefore have potential as a prognostic biomarker. Conversely, the pro-apoptotic function of IP6K2 has been proposed as a target to sensitize cancers to chemotherapeutic agents. In addition to cancers, IP6K2 signaling has been implicated in the etiology of neurodegenerative diseases and metabolic dysregulation. Dysregulation of inositol pyrophosphate signaling can alter neuronal cell death, energy homeostasis and stress responses.

Alternate Names for IP6K2

IP6K2; inositol hexakisphosphate kinase 2; PIUS; IHPK2; insp6 kinase 2; pi uptake stimulator; inositol hexaphosphate kinase 2; ATP:1D-myo-inositol-hexakisphosphate phosphotransferase;

• 1. Snyder SH. Mind molecules. J Biol Chem. 2011, 286(24):21023-32.