Using Drosophila eye as a model system to characterize the function of mars gene in cell-cycle regulation.
Human hepatoma up-regulated protein (HURP), a cell-cycle regulator, is found consistently overexpressed in human hepatocellular carcinoma. At present, the function of HURP in cell-cycle regulation and carcinogenesis remains unclear. In database mining, we have identified a mars gene in Drosophila, which encodes a protein with a high similarity to HURP in its guanylate kinase-associated protein (GKAP) motif. Overexpression but not down-regulation of mars in eye discs resulted in a higher mitotic index along with a high frequency of mitotic defects, including misalignment of chromosomes and mispositioned centrosomes, at the second mitotic wave (SMW). The consequence of mitotic defects impairs cell-cycle progression, and causes cell death posterior to the furrow. Immunocytochemical studies also have indicated that the expression of Mars is cell cycle regulated, and that its subcellular localization is dynamically changed during cell-cycle progression. Furthermore, we also demonstrated that the first 198 amino acids at the N-terminus of Mars are responsible for the degradation of Mars in non-mitotic cells. Together, we report the use Drosophila eye as a model system to characterize the function of the mars gene in cell-cycle regulation.
Yang
Ching-Po
CP
Department of Life Science and Life Science Research Center, Tunghai University, Taichung, 407 Taiwan, Republic of China.
Chen
Mei-Shu
MS
Liaw
Gwo-Jen
GJ
Chen
Shu-Fen
SF
Chou
Gash
G
Fan
Seng-Sheen
SS
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018385:Centrosome / Q000502:physiology; D015536:Down-Regulation; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005123:Eye / Q000166:cytology / Q000196:embryology / Q000378:metabolism* / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental; D005796:Genes; D017344:Genes, Insect; D007150:Immunohistochemistry; D008938:Mitosis / Q000502:physiology; D008954:Models, Biological; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D000074407:SAP90-PSD95 Associated Proteins; D017386:Sequence Homology, Amino Acid; D008941:Spindle Apparatus / Q000502:physiology; D019076:Transgenes
D018797:Cell Cycle Proteins; C000614187:DLGAP1 protein, human; D029721:Drosophila Proteins; C000614192:Mars protein, Drosophila; D009419:Nerve Tissue Proteins; D000074407:SAP90-PSD95 Associated Proteins