The ubiquitin ligase KBTBD8 regulates PKM1 levels via Erk1/2 and Aurora A to ensure oocyte quality

Aging
Yan-Ru LiZhi-Xia Yang

Abstract

Tight control of energy metabolism is essential for normal cell function and organism survival. PKM (pyruvate kinase, muscle) isoforms 1 and 2 originate from alternative splicing of PKM pre-mRNA. They are key enzymes in oxidative phosphorylation and aerobic glycolysis, respectively, and are essential for ATP generation. The PKM1:PKM2 expression ratio changes with development and differentiation, and may also vary under metabolic stress and other conditions. Until now, there have been no reports about the function and regulation of PKM isozymes in oocytes. Here, we demonstrate that PKM1 or PKM2 depletion significantly disrupts ATP levels and mitochondrial integrity, and exacerbates free-radical generation and apoptosis in mouse oocytes. We also show that KBTBD8, a female fertility factor in the KBTBD ubiquitin ligase family, selectively regulates PKM1 levels through a signaling cascade that includes Erk1/2 and Aurora A kinases as intermediates. Finally, using RNA sequencing and protein network analysis, we identify several regulatory proteins that may be govern generation of mature PKM1 mRNA. These results suggest KBTBD8 affects PKM1 levels in oocytes via a KBTBD8→Erk1/2→Aurora A axis, and may also affect other essential process...Continue Reading

References

Jun 11, 2009·Proceedings of the National Academy of Sciences of the United States of America·Luyang SunYongfeng Shang
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Cynthia V ClowerAdrian R Krainer
Aug 14, 2010·Cell·Michael J MoorePamela A Silver
Nov 27, 2010·American Journal of Human Genetics·Nyamkhishig SambuughinLev G Goldfarb
Feb 19, 2013·The International Journal of Developmental Biology·Esther Collado-FernandezRémi Dumollard
Aug 1, 2013·Proceedings of the National Academy of Sciences of the United States of America·Zhihua Gao, Thomas A Cooper
Oct 5, 2014·Cellular and Molecular Life Sciences : CMLS·Ling GuQiang Wang
Dec 9, 2014·Molecular Cell·Sophia Y LuntMatthew G Vander Heiden
Jan 23, 2015·Cellular and Molecular Life Sciences : CMLS·Takumi MikawaHiroshi Kondoh
Jun 17, 2015·Proceedings of the National Academy of Sciences of the United States of America·Kiran Kumar NakkaSamit Chattopadhyay
Apr 5, 2016·Oncogene·D RajendranC J McGlade
Nov 20, 2016·EMBO Reports·Talya L DaytonMatthew G Vander Heiden
Aug 23, 2017·ELife·Andres Ramirez-MartinezEric N Olson
Sep 6, 2017·The Journal of Clinical Investigation·James B PapizanEric N Olson
Feb 13, 2018·Cellular and Molecular Life Sciences : CMLS·Giel TangheWim Declercq
Jun 15, 2018·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Snehal N Chaudhari, Edward T Kipreos

❮ Previous
Next ❯

Citations

Sep 29, 2020·Journal of Cellular Biochemistry·Chun-Xiang ZhouZheng-Rong Xia
May 12, 2020·Cell Proliferation·Na-Na ZhangDong Zhang
Dec 10, 2019·Science China. Life Sciences·Lu WenZi-Jiang Chen
Jun 22, 2021·Frontiers in Cell and Developmental Biology·Yu WuMo Yang

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
Co-IP
CoIP
RNA-seq
ubiquitination
confocal microscopy
Assay

Software Mentioned

ImageJ

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Aging Genetics (Keystone)

This feed focuses on aging epidemiology and genetic, epigenetic, and proteomic aspects underlying aging, as well as aging- associated biomarkers. Here the latest research in this domain.