Regulation of protein phosphatase type 1 and cell cycle progression by PfLRR1, a novel leucine-rich repeat protein of the human malaria parasite Plasmodium falciparum.
The protein called 'suppressor of the dis2 mutant (sds22+)' is an essential regulator of cell division in fission and budding yeasts, where its deletion causes mitotic arrest. Its role in cell cycle control appears to be mediated through the activation of protein phosphatase type 1 (PP1) in Schizosaccharomyces pombe. We have identified the Plasmodium falciparum Sds22 orthologue, which we designated PfLRR1 as it belongs to the leucine-rich repeat protein family. We showed by glutathione-S-transferase pull-down assay that the PfLRR1 gene product interacts with PfPP1, that the PfLRR1-PfPP1 complex is present in parasite extracts and that PfLRR1 inhibits PfPP1 activity. Functional studies in Xenopus oocytes revealed that PfLRR1 interacted with endogenous PP1 and overcame the G2/M cell cycle checkpoint by promoting progression to germinal vesicle breakdown (GVBD). Confirmatory results showing the appearance of GVBD were observed when oocytes were treated with anti-PP1 antibodies or okadaic acid. Taken together, these observations suggest that PfLRR1 can regulate the cell cycle by binding to PP1 and regulating its activity.
Daher
Wassim
W
Unité Inserm 547/IPL, Institut Pasteur, 1 rue du Pr Calmette, B.P. 245, 59019 Lille cedex, France.
Browaeys
Edith
E
Pierrot
Christine
C
Jouin
Hélène
H
Dive
Daniel
D
Meurice
Edwige
E
Dissous
Colette
C
Capron
Monique
M
Tomavo
Stanislas
S
Doerig
Christian
C
Cailliau
Katia
K
Khalife
Jamal
J
D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D000090263:Leucine-Rich Repeat Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics; D009865:Oocytes; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000166:cytology*; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014981:Xenopus
D018797:Cell Cycle Proteins; D000090263:Leucine-Rich Repeat Proteins; D009687:Nuclear Proteins; D011506:Proteins; D029702:Schizosaccharomyces pombe Proteins; C066843:sds22 protein, S pombe; D010749:Phosphoprotein Phosphatases