Refereed journal article or data article (A1)

PIM kinases phosphorylate lactate dehydrogenase A at serine 161 and suppress its nuclear ubiquitination

List of AuthorsMung Kwan Long, Meinander Annika, Koskinen Päivi J.


Publication year2022

JournalFEBS Journal

Journal acronymFEBS J

Number of pages14





Self-archived copy’s web address

Lactate dehydrogenase A (LDHA) is a glycolytic enzyme catalysing the reversible conversion of pyruvate to lactate. It has been implicated as a substrate for PIM kinases, yet the relevant target sites and functional consequences of phosphorylation have remained unknown. Here, we show that all three PIM family members can phosphorylate LDHA at serine 161. When we investigated the physiological consequences of this phosphorylation in PC3 prostate cancer and MCF7 breast cancer cells, we noticed that it suppressed ubiquitin-mediated degradation of nuclear LDHA and promoted interactions between LDHA and 14-3-3 proteins. By contrast, in CRISPR/Cas9-edited knock-out cells lacking all three PIM family members, ubiquitination of nuclear LDHA was dramatically increased followed by its decreased expression. Our data suggest that PIM kinases support nuclear LDHA expression and activities by promoting phosphorylation-dependent interactions of LDHA with 14-3-3 epsilon, which shields nuclear LDHA from ubiquitin-mediated degradation.

Downloadable publication

This is an electronic reprint of the original article.
This reprint may differ from the original in pagination and typographic detail. Please cite the original version.

Last updated on 2022-21-12 at 09:12