PPIP5K1 Suppresses Etoposide-triggered Apoptosis.

Inositol hexakisphosphate kinase 2 (IP6K2) potentiates pro-apoptotic signalling and increases the sensitivity of mammalian cells to cytotoxic agents. Diphosphoinositol pentakisphosphate kinase (PPIP5K) generates inositol pyrophosphates (InsPPs) that are structurally distinct from those produced by IP6K2 and their possible roles in affecting cell viability remain unclear. In the present study, we tested the impact of PPIP5K1 on cellular sensitivity to various genotoxic agents to determine if PPIP5K1 and IP6K2 contribute similarly to apoptosis.

Mass spectrometry analysis of PPIP5K1 interactions and data on cell motility of PPIP5K1-deficient cells.

Inositol pyrophosphates are cellular signals that are created by the actions of inositol kinases and are degraded by highly active inositol phosphatases. The potent actions of these phosphatases suggest these signals must be created near their sites of action. To identify sites where the inositol kinase, PPIP5K1 acts, we performed affinity purification of PPIP5K1 from HEK293 cells and analyzed these samples using mass spectrometry to identify the proteins pesent (10.

Inhibition of carbonic anhydrase IX in glioblastoma multiforme.

Carbonic anhydrase IX (CAIX) is a transmembrane enzyme upregulated in several types of tumors including glioblastoma multiforme (GBM). GBM is among the most aggressive tumors among gliomas. Temozolomide (TMZ) therapy combined with surgical or radiation approaches is the standard treatment but not effective in long term.

PPIP5K1 interacts with the exocyst complex through a C-terminal intrinsically disordered domain and regulates cell motility.

Cellular signaling involves coordinated regulation of many events. Scaffolding proteins are crucial regulators of cellular signaling, because they are able to affect numerous events by coordinating specific interactions among multiple protein partners in the same pathway. Scaffolding proteins often contain intrinsically disordered regions (IDR) that facilitate the formation and function of distinct protein complexes.

Effect of calorie restriction on the metabolic history of chronologically aging yeast.

Aging is a highly complex, multifactorial process. We use the yeast Saccharomyces cerevisiae as a model to study the mechanisms of cellular aging in multicellular eukaryotes. To address the inherent complexity of aging from a systems perspective and to build an integrative model of aging process, we investigated the effect of calorie restriction (CR), a low-calorie dietary regimen, on the metabolic history of chronologically aging yeast.