Small ubiquitin-related modifier paralogs are indispensable but functionally redundant during early development of zebrafish.
The Small ubiquitin-related modifier (SUMO) conjugation to a variety of proteins regulates diverse cellular processes, including transcription, cell cycle regulation and maintenance of genome integrity. To investigate in vivo biological function of SUMO paralogs, we inactivated them in the early development of zebrafish. While zebrafish embryos deficient for all three SUMO paralogs, as Ubc9-deficient ones, displayed severe defects, loss of individual SUMO paralog was compatible with a normal development. SUMO-deficient embryos can be rescued by a single human or zebrafish SUMO. While key structural basic lysine residues and N-terminal unstructured stretch of SUMO are critical for in vivo rescue, the consensus K11 sumoylation site of SUMO2 is dispensable, implying that chain formation on this potential site is unessential for normal development. Inactivation of all three SUMOs triggered p53-dependent apoptosis and further inactivation of p53 restored normal zebrafish development. Interestingly, we also demonstrate that the dominant negative truncated form of p53, Delta113p53, significantly blunts SUMO depletion-induced p53 activity in vivo. Taken together, our results suggest that SUMO paralogs are indispensable, but redundant, in the early development of zebrafish.
Yuan
Hao
H
State Key Laboratory of Medical Genomics, Institute of Health Science, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Zhou
Jun
J
Deng
Min
M
Liu
Xi
X
Le Bras
Morgane
M
de The
Hugues
H
Chen
Sai Juan
SJ
Chen
Zhu
Z
Liu
Ting Xi
TX
Zhu
Jun
J
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000235:genetics*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D005816:Genetic Complementation Test; D006801:Humans; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011499:Protein Processing, Post-Translational / Q000235:genetics; D017385:Sequence Homology; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism
D025841:Small Ubiquitin-Related Modifier Proteins