Characterization of tlk-1 function in mitosis in C. elegans
Date Issued
2004
Date
2004
Author(s)
Yang, Hui-Ju
DOI
en-US
Abstract
Faithful chromosome segregation during mitosis assure the transmission of genetic information and this event is much dependent on protein proteolysis. This thesis shows that TLK-1, a protein encodes serine/threonine kinase, plays key roles on mitosis and regulated by degradation. The tlk-1(RNAi) mutants arrested at about 50-cell stage showing the phenotype of aneupolidy and DNA bridge. TLK-1 protein was expressed in a cell-cycle-dependent manner. It is detected in interphase and prophase nuclei but not in mitotic cells from metaphase through anaphase. As TLK-1 harbors two D-box motifs, which are anaphase-promoting complex (APC)-dependent proteolysis signals, we investigated if these motifs are important for the dramatic disappearance of TLK-1 at metaphase. Mutations in D-box motifs caused the persistent presence of TLK-1 at metaphase, indicating that D box motifs are required for the degradation of TLK-1 at metaphase. The C. elegans mat-2 and emb-30 encodes subunits of APC. When any of these genes is mutated, TLK-1 protein is abnormally present at metaphase. The C. elegans AIR-2, Aurora/Ipl1-related Kinases, associates with chromosome and midbody microtubules is required for chromosome segregation. We further examined TLK-1 localization under air-2(RNAi) background; intriguingly, TLK-1 was found associated with metaphase chromosome. In addition to tlk-1 loss-of–function causing dead embryos, we found tlk-1 overexpression can also lead to embryonic lethal. Supposedly, the amount of TLK-1 in normal cells is tightly controlled in balance. The human homologue of TLK-1 can partially rescue the tlk-1(RNAi) mutant embryos, indicating that the function of tlk-1 is evolutionary functional conserved.
Subjects
後期促進複合體
擬混亂激酶
有絲分裂
線蟲
染色體分離
TLK-1
AIR-2
aneuploidy
mitosis
anaphase-promoting complex
chromosome segregation
Type
other
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