The SUMO pathway is essential for nuclear integrity and chromosome segregation in mice.
Covalent modification by SUMO regulates a wide range of cellular processes, including transcription, cell cycle, and chromatin dynamics. To address the biological function of the SUMO pathway in mammals, we generated mice deficient for the SUMO E2-conjugating enzyme Ubc9. Ubc9-deficient embryos die at the early postimplantation stage. In culture, Ubc9 mutant blastocysts are viable, but fail to expand after 2 days and show apoptosis of the inner cell mass. Loss of Ubc9 leads to major chromosome condensation and segregation defects. Ubc9-deficient cells also show severe defects in nuclear organization, including nuclear envelope dysmorphy and disruption of nucleoli and PML nuclear bodies. Moreover, RanGAP1 fails to accumulate at the nuclear pore complex in mutant cells that show a collapse in Ran distribution. Together, these findings reveal a major role for Ubc9, and, by implication, for the SUMO pathway, in nuclear architecture and function, chromosome segregation, and embryonic viability in mammals.
Nacerddine
Karim
K
Unité d'Organisation Nucléaire et Oncogénèse, INSERM U 579, Institut Pasteur, 75724 Paris Cedex 15, France.
Lehembre
François
F
Bhaumik
Mantu
M
Artus
Jérôme
J
Cohen-Tannoudji
Michel
M
Babinet
Charles
C
Pandolfi
Pier Paolo
PP
Dejean
Anne
A
D000818:Animals; D017209:Apoptosis; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D020964:Embryo Loss / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D020690:GTPase-Activating Proteins / Q000378:metabolism; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008938:Mitosis; D015398:Signal Transduction; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000502:physiology*; D014452:Ubiquitins / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D020690:GTPase-Activating Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D014452:Ubiquitins; D044763:Ubiquitin-Conjugating Enzymes; D020931:ran GTP-Binding Protein; D000098843:Ubiquitin-Conjugating Enzyme UBC9