RT Journal Article
T1 Exploration of nuclear body-enhanced sumoylation reveals that PML represses 2-cell features of embryonic stem cells.
A1 Tessier, Sarah
A1 Ferhi, Omar
A1 Geoffroy, Marie-Claude
A1 González-Prieto, Román
A1 Canat, Antoine
A1 Quentin, Samuel
A1 Pla, Marika
A1 Niwa-Kawakita, Michiko
A1 Bercier, Pierre
A1 Rérolle, Domitille
A1 Tirard, Marilyn
A1 Therizols, Pierre
A1 Fabre, Emmanuelle
A1 Vertegaal, Alfred C O
A1 de Thé, Hugues
A1 Lallemand-Breitenbach, Valérie
AB Membrane-less organelles are condensates formed by phase separation whose functions often remain enigmatic. Upon oxidative stress, PML scaffolds Nuclear Bodies (NBs) to regulate senescence or metabolic adaptation. PML NBs recruit many partner proteins, but the actual biochemical mechanism underlying their pleiotropic functions remains elusive. Similarly, PML role in embryonic stem cell (ESC) and retro-element biology is unsettled. Here we demonstrate that PML is essential for oxidative stress-driven partner SUMO2/3 conjugation in mouse ESCs (mESCs) or leukemia, a process often followed by their poly-ubiquitination and degradation. Functionally, PML is required for stress responses in mESCs. Differential proteomics unravel the KAP1 complex as a PML NB-dependent SUMO2-target in arsenic-treated APL mice or mESCs. PML-driven KAP1 sumoylation enables activation of this key epigenetic repressor implicated in retro-element silencing. Accordingly, Pml-/- mESCs re-express transposable elements and display 2-Cell-Like features, the latter enforced by PML-controlled SUMO2-conjugation of DPPA2. Thus, PML orchestrates mESC state by coordinating SUMO2-conjugation of different transcriptional regulators, raising new hypotheses about PML roles in cancer.
YR 2022
FD 2022-09-29
LK http://hdl.handle.net/10668/19546
UL http://hdl.handle.net/10668/19546
LA en
DS RISalud
RD Apr 12, 2025