title: The cyclomodulin Cif of Photorhabdus luminescens inhibits insect cell proliferation and triggers host cell death by apoptosis.
abstract: Cycle inhibiting factors (Cif) constitute a broad family of cyclomodulins present in bacterial pathogens of invertebrates and mammals. Cif proteins are thought to be type III effectors capable of arresting the cell cycle at G(2)/M phase transition in human cell lines. We report here the first direct functional analysis of Cif(Pl), from the entomopathogenic bacterium Photorhabdus luminescens, in its insect host. The cif(Pl) gene was expressed in P. luminescens cultures in vitro. The resulting protein was released into the culture medium, unlike the well characterized type III effector LopT. During locust infection, cif(Pl) was expressed in both the hemolymph and the hematopoietic organ, but was not essential for P. luminescens virulence. Cif(Pl) inhibited proliferation of the insect cell line Sf9, by blocking the cell cycle at the G(2)/M phase transition. It also triggered host cell death by apoptosis. The integrity of the Cif(Pl) catalytic triad is essential for the cell cycle arrest and pro-apoptotic activities of this protein. These results highlight, for the first time, the dual role of Cif in the control of host cell proliferation and apoptotic death in a non-mammalian cell line.
authors.affiliation: INRA, UMR 1133, Laboratoire EMIP, Montpellier, France; Université Montpellier 2, UMR 1133, Laboratoire EMIP, Montpellier, France.
authors.forename: Carolina Varela
authors.initials: CV
authors.lastname: Chavez
authors.forename: Grégory
authors.initials: G
authors.lastname: Jubelin
authors.forename: Gabriel
authors.initials: G
authors.lastname: Courties
authors.forename: Aurélie
authors.initials: A
authors.lastname: Gomard
authors.forename: Nadège
authors.initials: N
authors.lastname: Ginibre
authors.forename: Sylvie
authors.initials: S
authors.lastname: Pages
authors.forename: Frédéric
authors.initials: F
authors.lastname: Taïeb
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Girard
authors.forename: Eric
authors.initials: E
authors.lastname: Oswald
authors.forename: Alain
authors.initials: A
authors.lastname: Givaudan
authors.forename: Robert
authors.initials: R
authors.lastname: Zumbihl
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Escoubas
mesh_terms: D000825:Animal Structures / Q000382:microbiology; D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D006110:Grasshoppers / Q000382:microbiology*; D006458:Hemolymph / Q000382:microbiology; D020637:Photorhabdus / Q000472:pathogenicity*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors