title: CCR4-associated factor 1 coordinates the expression of Plasmodium falciparum egress and invasion proteins.
abstract: Coordinated regulation of gene expression is a hallmark of the Plasmodium falciparum asexual blood-stage development cycle. We report that carbon catabolite repressor protein 4 (CCR4)-associated factor 1 (CAF1) is critical in regulating more than 1,000 genes during malaria parasites' intraerythrocytic stages, especially egress and invasion proteins. CAF1 knockout results in mistimed expression, aberrant accumulation and localization of proteins involved in parasite egress, and invasion of new host cells, leading to premature release of predominantly half-finished merozoites, drastically reducing the intraerythrocytic growth rate of the parasite. This study demonstrates that CAF1 of the CCR4-Not complex is a significant gene regulatory mechanism needed for Plasmodium development within the human host.
authors.affiliation: Department of Global Health, College of Public Health, University of South Florida, College of Public Health, 3720 Spectrum Blvd., Suite 304, Tampa, FL, USA.
authors.forename: Bharath
authors.initials: B
authors.lastname: Balu
authors.forename: Steven P
authors.initials: SP
authors.lastname: Maher
authors.forename: Alena
authors.initials: A
authors.lastname: Pance
authors.forename: Chitra
authors.initials: C
authors.lastname: Chauhan
authors.forename: Anatoli V
authors.initials: AV
authors.lastname: Naumov
authors.forename: Robert M
authors.initials: RM
authors.lastname: Andrews
authors.forename: Peter D
authors.initials: PD
authors.lastname: Ellis
authors.forename: Shahid M
authors.initials: SM
authors.lastname: Khan
authors.forename: Jing-Wen
authors.initials: JW
authors.lastname: Lin
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Janse
authors.forename: Julian C
authors.initials: JC
authors.lastname: Rayner
authors.forename: John H
authors.initials: JH
authors.lastname: Adams
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004912:Erythrocytes / Q000469:parasitology* / Q000473:pathology; D017353:Gene Deletion; D015870:Gene Expression; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006790:Host-Parasite Interactions / Q000235:genetics*; D006801:Humans; D008018:Life Cycle Stages; D016778:Malaria, Falciparum / Q000469:parasitology; D052940:Merozoites / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D014157:Transcription Factors