Characterization of Schistosoma mansoni Sds homologue, a leucine-rich repeat protein that interacts with protein phosphatase type 1 and interrupts a G2/M cell-cycle checkpoint.
The suppressor of the dis2 mutant (sds22+) has been shown to be an essential regulator in cell division of fission and budding yeast where its deletion causes mitotic arrest. Its role seems to take place through the activation of PP1 (protein phosphatase type 1) in Schizosaccharomyces pombe. In the trematode Schistosoma mansoni, we have identified the Sds22 homologue (SmSds), and the PP1 (SmPP1). We showed by using a GST (glutathione S-transferase) pull-down assay that the SmSds gene product interacts with SmPP1 and that the SmSds-SmPP1 complex is present in parasite extracts. Furthermore, we observed that SmSds inhibited PP1 activity. Functional studies showed that the microinjection of SmSds into Xenopus oocytes interacted with the Xenopus PP1 and disrupted the G2/M cell-cycle checkpoint by promoting progression to GVBD (germinal vesicle breakdown). Similar results showing the appearance of GVBD were observed when oocytes were treated with anti-PP1 antibodies. Taken together, these observations suggest that SmSds can regulate the cell cycle by binding to PP1.
Daher
Wassim
W
Unité INSERM 547/IPL, Institut Pasteur, 1 rue du Pr Calmette, B.P. 245, F-59019 Lille Cedex, France.
Cailliau
Katia
K
Takeda
Kojiro
K
Pierrot
Christine
C
Khayath
Naji
N
Dissous
Colette
C
Capron
Monique
M
Yanagida
Mitsuhiro
M
Browaeys
Edith
E
Khalife
Jamal
J
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology*; D002457:Cell Extracts; D016195:G2 Phase / Q000502:physiology*; D005816:Genetic Complementation Test; D005982:Glutathione Transferase / Q000378:metabolism; D015801:Helminth Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D000090263:Leucine-Rich Repeat Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D012550:Schistosoma mansoni / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D016415:Sequence Alignment; D014981:Xenopus
D018797:Cell Cycle Proteins; D002457:Cell Extracts; D015801:Helminth Proteins; D000090263:Leucine-Rich Repeat Proteins; D009687:Nuclear Proteins; D011506:Proteins; D011994:Recombinant Proteins; D029702:Schizosaccharomyces pombe Proteins; C066843:sds22 protein, S pombe; D005982:Glutathione Transferase; D010749:Phosphoprotein Phosphatases