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Characterization of two nima interacting proteins suggests a link between nima and nuclear membrane fission

Davies, Jonathan Robert

Abstract Details

2004, Doctor of Philosophy, Ohio State University, Molecular Genetics.
In the filamentous fungus Aspergillus nidulans, the NIMA kinase is required along with CDK1/cyclinB for mitotic entry. The essential function of NIMA in A. nidulans and the growing recognition of its importance in other eukaryotes, means that the study of NIMA function should reveal unique insights into cell cycle regulation amongst a broad range of organisms. I describe here the characterization of TINC and TIND, two NIMA interacting proteins identified in a yeast Two-hybrid screen, and describe the potential novel roles they may play in mitotic regulation. TINC and a related protein in A. nidulans, An-HETC, are highly similar to proteins conserved in filamentous fungi. Strains which lack both tinC and An-hetC are viable, but do display osmotic and cold sensitivity. Characterization of TINC suggests that it is involved in mitotic regulation. First, TINC is present in the nucleus during mitosis. Second, TINC interacts with NIMA in a phosphorylation state dependant manner. Third, truncated forms of TINC (ΔN-TINC) produce cell cycle defects characterized by a defect in nuclear membrane fission in which cells are able to separate DNA but unable to cleave the nuclear envelope. Significantly, ΔN-TINC localizes to membranous bodies which associate with nuclei. Finally, expression of ΔN-TINC promotes premature loss of NIMA from mitotic samples. The second NIMA interacting protein, TIND, is conserved from bacteria through to humans. TIND is predominantly mitochondrial throughout the cell cycle, but work in other organisms suggests that alternate forms of TIND may exist outside the mitochondria. Expression of a form of TIND which lacks the mitochondrial targeting peptide (ΔN-TIND) produces nuclear division and nuclear membrane fission defects similar to those seen for ΔN-TINC. Additionally, ΔN-TIND also produces defective mitotic spindles, which appear monopolar, an effect not seen for ΔN-TINC. The facts that TINC and TIND were isolated as NIMA interacting proteins, TINC interacts with NIMA in A. nidulans, and expression of ΔN-TINC or ΔN-TIND produces specific defects in nuclear membrane fission suggest roles for these proteins in mitotic regulation. Additionally, the finding that NIMA is destabilized in cells displaying mitotic defects suggests a role for NIMA in regulating nuclear membrane fission.
Stephen Osmani (Advisor)
216 p.

Recommended Citations

Citations

  • Davies, J. R. (2004). Characterization of two nima interacting proteins suggests a link between nima and nuclear membrane fission [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1091649681

    APA Style (7th edition)

  • Davies, Jonathan. Characterization of two nima interacting proteins suggests a link between nima and nuclear membrane fission. 2004. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1091649681.

    MLA Style (8th edition)

  • Davies, Jonathan. "Characterization of two nima interacting proteins suggests a link between nima and nuclear membrane fission." Doctoral dissertation, Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=osu1091649681

    Chicago Manual of Style (17th edition)