The trypanosome-specific proteins FPRC and CIF4 regulate cytokinesis initiation by recruiting CIF1 to the cytokinesis initiation site [Microbiology]

September 20th, 2019 by Huiqing Hu, Tai An, Yasuhiro Kurasawa, Qing Zhou, Ziyin Li

The evolutionarily early divergent human parasite Trypanosoma brucei proliferates through binary cell fission in both its tsetse fly vector and mammalian host. The parasite divides uni-directionally along the longitudinal cell axis from the anterior cell tip toward the posterior cell tip through a mechanism distinct from that in the cells of its human host. Initiation of cytokinesis in T. brucei is regulated by two evolutionarily conserved protein kinases, the Polo-like kinase TbPLK and the Aurora B kinase TbAUK1, and a cohort of trypanosome-specific proteins, including three cytokinesis initiation factors CIF1, CIF2, and CIF3. Here, using RNA interference, in situ epitope tagging of proteins, GST pull-down and co-immunoprecipitation assays, and immunofluorescence and scanning EM microscopy analyses, we report the identification and functional characterization of two trypanosome-specific proteins, FPRC and CIF4. We found that the two proteins co-localize to the distal tips of the new and the old flagellum attachment zones, and are required for cytokinesis initiation. Knockdown of FPRC or CIF4 each disrupted the localization of CIF1, suggesting that they function upstream of CIF1. Moreover, depletion of CIF4 abolished FPRC localization, indicating that CIF4 acts upstream of FPRC. Together, these results identify two new cytokinesis regulators in T. brucei and integrate them into the CIF1-mediated cytokinesis regulatory pathway. These findings highlight the existence of a cytokinesis pathway in T. brucei that is different from that of its mammalian host and therefore suggest that cytokinesis in T. brucei could potentially be exploited as a new drug target.
  • Posted in Journal of Biological Chemistry, Publications
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Colibactin comes to light

September 20th, 2019 by Caitlin Deane

Nature Chemical Biology, Published online: 20 September 2019; doi:10.1038/s41589-019-0373-8

Colibactin comes to light

First contact

September 20th, 2019 by Yiyun Song

Nature Chemical Biology, Published online: 20 September 2019; doi:10.1038/s41589-019-0375-6

First contact

A NAMe-tag for ALS

September 20th, 2019 by Mirella Bucci

Nature Chemical Biology, Published online: 20 September 2019; doi:10.1038/s41589-019-0374-7

A NAMe-tag for ALS

The root of the cause

September 20th, 2019 by Grant Miura

Nature Chemical Biology, Published online: 20 September 2019; doi:10.1038/s41589-019-0376-5

The root of the cause

[ASAP] Improving Chromosome Synthesis with a Semiquantitative Phenotypic Assay and Refined Assembly Strategy

September 19th, 2019 by

TOC Graphic

ACS Synthetic Biology
DOI: 10.1021/acssynbio.8b00505
  • Posted in ACS Synthetic Biology, Publications
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Versatile biomanufacturing through stimulus-responsive cell–material feedback

September 16th, 2019 by Zhuojun Dai

Nature Chemical Biology, Published online: 16 September 2019; doi:10.1038/s41589-019-0357-8

Encapsulation of engineered bacteria in environmentally responsive materials enables on-demand protein production coupled to downstream processes such as protein purification, on-chip enzyme kinetics and metabolic production of fatty acids.
  • Posted in Nat Chem Biol, Publications
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Development of targeted protein degradation therapeutics

September 16th, 2019 by Philip P. Chamberlain

Nature Chemical Biology, Published online: 16 September 2019; doi:10.1038/s41589-019-0362-y

This Perspective summarizes recent discoveries that have laid the foundation for targeted degradation therapeutics and discusses the current state of understanding and consideration involved in developing these protein degraders.

DNA repair complex licenses acetylation of H2A.Z.1 by KAT2A during transcription

September 16th, 2019 by M. Semer

Nature Chemical Biology, Published online: 16 September 2019; doi:10.1038/s41589-019-0354-y

KAT2A acetylates histone variant H2A.Z to regulate transactivation of XPC and RAR positively regulated genes. The DNA repair complex XPC–RAD23–CEN2 interacts with H2A.Z and KAT2A to license the latter’s histone acetyltransferase activity.
  • Posted in Nat Chem Biol, Publications
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[ASAP] Scalable Chemoenzymatic Synthesis of Inositol Pyrophosphates

September 13th, 2019 by

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Biochemistry
DOI: 10.1021/acs.biochem.9b00587