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Review
. 2024 Jan 26;14(2):152.
doi: 10.3390/biom14020152.

Kcs1 and Vip1: The Key Enzymes behind Inositol Pyrophosphate Signaling in Saccharomyces cerevisiae

Larisa Ioana Gogianu  1   2 , Lavinia Liliana Ruta  3 , Ileana Cornelia Farcasanu  1   3
Affiliations
Review

Kcs1 and Vip1: The Key Enzymes behind Inositol Pyrophosphate Signaling in Saccharomyces cerevisiae

Larisa Ioana Gogianu et al. Biomolecules. .

Abstract

The inositol pyrophosphate pathway, a complex cell signaling network, plays a pivotal role in orchestrating vital cellular processes in the budding yeast, where it regulates cell cycle progression, growth, endocytosis, exocytosis, apoptosis, telomere elongation, ribosome biogenesis, and stress responses. This pathway has gained significant attention in pharmacology and medicine due to its role in generating inositol pyrophosphates, which serve as crucial signaling molecules not only in yeast, but also in higher eukaryotes. As targets for therapeutic development, genetic modifications within this pathway hold promise for disease treatment strategies, offering practical applications in biotechnology. The model organism Saccharomyces cerevisiae, renowned for its genetic tractability, has been instrumental in various studies related to the inositol pyrophosphate pathway. This review is focused on the Kcs1 and Vip1, the two enzymes involved in the biosynthesis of inositol pyrophosphate in S. cerevisiae, highlighting their roles in various cell processes, and providing an up-to-date overview of their relationship with phosphate homeostasis. Moreover, the review underscores the potential applications of these findings in the realms of medicine and biotechnology, highlighting the profound implications of comprehending this intricate signaling network.

Keywords: Kcs1; Saccharomyces cerevisiae; Vip1; inositol hexakisphosphate kinase; inositol pyrophosphate.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 2
Figure 2
Synthesis of PP-Ips in yeast: In Saccharomyces cerevisiae, Kcs1 and Vip1 are the only inositol hexakisphosphate kinases (IP6K) described to date, both synthesizing PP-Ips primarily from IP6. Kcs1 adds a phosphate group at position 5, participating in the synthesis of 5PP-IP4 from IP5, 5PP-IP5 from IP6, and 1,5PP-IP4 from 1PP-IP5. Kcs1 action is reversed by Siw16 pyrophosphatase. Vip1 acts both as a kinase and pyrophosphatase, adding and removing phosphate from position 1; as a kinase, Vip1 participates in the synthesis of 1PP-IP5 from IP6 and 1,5PP-IP4 from 5PP-IP5. The kinase activity of Vip1 is reversed by Ddp1 pyrophosphatase (based on [1,20]).
Figure 1
Figure 1
The multiple roles of Kcs1 and Vip1 in the cell processes of Saccharomyces cerevisiae.
Figure 3
Figure 3
The PHO pathway modulation by PP-IPs: (a) in low-[Pi] conditions, Pho81 inhibits the Pho85–Pho80 complex, leaving Pho4 free to activate the transcription of PHO genes; (b) in high-[Pi] conditions, PP-IPs bind to Pho81, inhibiting its interaction with the Pho85–Pho80 complex; phosphorylated Pho4 is exported outside the nucleus and the PHO genes’ transcription remains inactivated (based on [32,33]).
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