This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ipl1 regulation of the Ase1 and Kip3 proteins Chris Breed, Chitra Kotwaliwale and Sue Biggins Fred Hutchinson Cancer Research Center Chromosomes must accurately segregate to daughter cells to prevent genomic instability and aneuploidy, a hallmark of all tumors. A key regulator of chromosome segregation is Ipl1, the budding yeast homolog of the conserved Aurora protein kinase family. We have found that Ipl1 has roles in kinetochore biorientation, spindle assembly and spindle disassembly. Despite its critical role in multiple processes related to chromosome segregation, the key targets that Ipl1 regulates for these functions are unknown. We have identified two excellent candidate proteins that Ipl1 may regulate to mediate its functions in spindle assembly and spindle disassembly. Because the overexpression of the Ase1 protein suppresses the ipl1 mutant phenotype in spindle assembly, we mutated the five Ipl1 consensus phosphorylation sites in Ase1 (Ase1-5A). Strikingly, the Ase1-5A mutant has the same spindle assembly defects as an ipl1 mutant. Taken together, these data strongly suggest that Ipl1 may phosphorylate Ase1 to regulate spindle assembly. Similarly, we have found a single Ipl1 consensus site mutation in the Kip3 motor protein phenocopies the ipl1 mutant defect in spindle disassembly. In addition, Ipl1 can phosphorylate Ase1 and Kip3 in vitro. Because these studies suggest that Ase1 and Kip3 may be key targets of Ipl1, we propose to determine whether Ase1 and Kip3 are phosphorylated on the Ipl1 consensus sites in vivo.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
2P41RR011823-11
Application #
7420766
Study Section
Special Emphasis Panel (ZRG1-CB-H (40))
Project Start
2006-09-20
Project End
2007-08-31
Budget Start
2006-09-20
Budget End
2007-08-31
Support Year
11
Fiscal Year
2006
Total Cost
$2,859
Indirect Cost
Name
University of Washington
Department
Biochemistry
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Xavier, Marina Amaral; Tirloni, Lucas; Pinto, Antônio F M et al. (2018) A proteomic insight into vitellogenesis during tick ovary maturation. Sci Rep 8:4698
Hollmann, Taylor; Kim, Tae Kwon; Tirloni, Lucas et al. (2018) Identification and characterization of proteins in the Amblyomma americanum tick cement cone. Int J Parasitol 48:211-224
Stieg, David C; Willis, Stephen D; Ganesan, Vidyaramanan et al. (2018) A complex molecular switch directs stress-induced cyclin C nuclear release through SCFGrr1-mediated degradation of Med13. Mol Biol Cell 29:363-375
Seixas, Adriana; Alzugaray, María Fernanda; Tirloni, Lucas et al. (2018) Expression profile of Rhipicephalus microplus vitellogenin receptor during oogenesis. Ticks Tick Borne Dis 9:72-81
Wang, Zheng; Wu, Catherine; Aslanian, Aaron et al. (2018) Defective RNA polymerase III is negatively regulated by the SUMO-Ubiquitin-Cdc48 pathway. Elife 7:
Luhtala, Natalie; Aslanian, Aaron; Yates 3rd, John R et al. (2017) Secreted Glioblastoma Nanovesicles Contain Intracellular Signaling Proteins and Active Ras Incorporated in a Farnesylation-dependent Manner. J Biol Chem 292:611-628
Thakar, Sonal; Wang, Liqing; Yu, Ting et al. (2017) Evidence for opposing roles of Celsr3 and Vangl2 in glutamatergic synapse formation. Proc Natl Acad Sci U S A 114:E610-E618
Jin, Meiyan; Fuller, Gregory G; Han, Ting et al. (2017) Glycolytic Enzymes Coalesce in G Bodies under Hypoxic Stress. Cell Rep 20:895-908
Ogami, Koichi; Richard, Patricia; Chen, Yaqiong et al. (2017) An Mtr4/ZFC3H1 complex facilitates turnover of unstable nuclear RNAs to prevent their cytoplasmic transport and global translational repression. Genes Dev 31:1257-1271
Ju Lee, Hyun; Bartsch, Deniz; Xiao, Cally et al. (2017) A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells. Nat Commun 8:1456

Showing the most recent 10 out of 583 publications