PHGDH supports liver ceramide synthesis and sustains lipid homeostasis.

ABSTRACT:

Background

d-3-phosphoglycerate dehydrogenase (PHGDH), which encodes the first enzyme in serine biosynthesis, is overexpressed in human cancers and has been proposed as a drug target. However, whether PHGDH is critical for the proliferation or homeostasis of tissues following the postnatal period is unknown.

Methods

To study PHGDH inhibition in adult animals, we developed a knock-in mouse model harboring a PHGDH shRNA under the control of a doxycycline-inducible promoter. With this model, PHGDH depletion can be globally induced in adult animals, while sparing the brain due to poor doxycycline delivery.

Results

We found that PHGDH depletion is well tolerated, and no overt phenotypes were observed in multiple highly proliferative cell compartments. Further, despite dete

SUBMITTER: Kang YP 

PROVIDER: S-EPMC7294658 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature