Asymmetric mitosis: Unequal segregation of proteins destined for degradation.
Mitotic cell division ensures that two daughter somatic cells inherit identical genetic material. Previous work has shown that signaling by the Smad1 transcription factor is terminated by polyubiquitinylation and proteasomal degradation after essential phosphorylations by MAPK and glycogen synthase kinase 3 (GSK3). Here, we show that, unexpectedly, proteins specifically targeted for proteasomal degradation are inherited preferentially by one mitotic daughter during somatic cell division. Experiments with dividing human embryonic stem cells and other mammalian cultured cell lines demonstrated that in many supposedly equal mitoses the segregation of proteins destined for degradation (Smad1 phosphorylated by MAPK and GSK3, phospho-beta-catenin, and total polyubiquitinylated proteins) was asymmetric. Transport of pSmad1 targeted for degradation to the centrosome required functional microtubules. In vivo, an antibody specific for Mad phosphorylated by MAPK showed that this antigen was associated preferentially with one of the two centrosomes in Drosophila embryos at cellular blastoderm stage. We propose that this remarkable cellular property may be explained by the asymmetric inheritance of peripheral centrosomal proteins when centrioles separate and migrate to opposite poles of the cell, so that one mitotic daughter remains pristine. We conclude that many mitotic divisions are unequal, unlike what was previously thought.
Fuentealba
Luis C
LC
Howard Hughes Medical Institute and Department of Biological Chemistry, University of California, Los Angeles, CA 90095-1662, USA.
Eivers
Edward
E
Geissert
Douglas
D
Taelman
Vincent
V
De Robertis
E M
EM
D000818:Animals; D001756:Blastoderm / Q000166:cytology / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D019556:COS Cells / Q000378:metabolism; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism; D002522:Chlorocebus aethiops; D004330:Drosophila / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D008938:Mitosis; D008954:Models, Biological; D010766:Phosphorylation; D025821:Polyubiquitin / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*; D051898:Smad1 Protein / Q000378:metabolism; D054875:Ubiquitination; D051176:beta Catenin / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; D011506:Proteins; D051898:Smad1 Protein; D051176:beta Catenin; D025821:Polyubiquitin; D038362:Glycogen Synthase Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D046988:Proteasome Endopeptidase Complex