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Einarson MB , Cukierman E , Compton DA , Golemis EA
Human enhancer of invasion-cluster, a coiled-coil protein required for passage through mitosis
Molecular and Cellular Biology. 2004 May;24(9) :3957-3971
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Abstract
In a cross-species overexpression approach, we used the pseudohyphal transition of Saccharomyces cerevisiae as a model screening system to identify human genes that regulate cell morphology and the cell cycle. Human enhancer of invasion-cluster (HEI-C), encoding a novel evolutionarily conserved coiled-coil protein, was isolated in a screen for human genes that induce agar invasion in S. cerevisiae. In human cells, HEI-C is primarily localized to the spindle during mitosis. Depletion of HEI-C in vivo with short interfering RNAs results in severe mitotic defects. Analysis by immunofluorescence, How cytometry analysis, and videomicroscopy indicates that HEI-C-depleted cells form metaphase plates with normal timing after G(2)/M transition, although in many cases cells have disorganized mitotic spindles. Subsequently, severe defects occur at the metaphase-anaphase transition, characterized by a significant delay at this stage or, more commonly, cellular disintegration accompanied! by the display of classic biochemical markers of apoptosis. These mitotic defects occur in spite of the fact that HEI-C-depleted cells retain functional cell cycle checkpoints, as these cells arrest normally following nocodazole or hydroxyurea treatment. These results place HEI-C as a novel regulator of spindle function and integrity during the metaphase-anaphase transition.
Notes
English Article KeyWords Plus: SPINDLE-ASSEMBLY CHECKPOINT; SACCHAROMYCES-CEREVISIAE; CELL-CYCLE; FILAMENTOUS GROWTH; DOCKING PROTEIN; CHROMOSOME ALIGNMENT; POTENTIAL EFFECTOR; CYTOPLASMIC DYNEIN; BUDDING YEAST; KINASE Golemis, EA; *Fox* *Chase* Canc Ctr, Div Basic Sci, W406,333 Cottman Ave, Philadelphia, PA 19111 USA. Research Addresses: *Fox* *Chase* Canc Ctr, Div Basic Sci, Philadelphia, PA 19111 USA. Dartmouth Coll, Sch Med, Dept Biochem, Hanover, NH 03755 USA. Cited References: AMON A, 1999, CURR OPIN GENET DEV, V9, P69 BARRAL Y, 1995, GENE DEV, V9, P399 BRAVERMAN LE, 1999, J BIOL CHEM, V274, P5542 BURNS TF, 2003, MOL CELL BIOL, V23, P5556 CHAN GK, 2003, PROG CELL CYCLE RES, V5, P431 CHEN CN, 2001, INT J NONLINEAR SCI, V2, P235 CLODI K, 2000, CYTOMETRY, V40, P19 COMPTON DA, 1998, METHOD ENZYMOL, V298, P331 COMPTON DA, 2000, ANNU REV BIOCHEM, V69, P95 DELUCA JG, 2002, J CELL BIOL, V159, P549 DENELZEN N, 2001, J CELL BIOL, V153, P121 DRUBIN DG, 1996, CELL, V84, P335 DUJARDIN D, 1998, J CELL BIOL, V141, P849 ELBASHIR SM, 2001, GENE DEV, V15, P188 FASHENA SJ, 2002, J CELL SCI, V115, P99 FLYNN P, 1998, J BIOL CHEM, V273, P2698 FORNEROD M, 1997, CELL, V90, P1051 FRASER AG, 1999, CURR BIOL, V9, P292 GAGLIO T, 1995, J CELL BIOL, V131, P693 GARBER AT, 1989, EMBO J, V8, P1727 GARRY R, 2002, GYNAECOL ENDOSC, V11, P5 GILLETT ES, 2001, DEV CELL, V1, P162 GIMENO CJ, 1992, CELL, V68, P1077 HAGTING A, 2002, J CELL BIOL, V157, P1125 HARDWICK KG, 1995, J CELL BIOL, V131, P709 HERBERT M, 2003, NAT CELL BIOL, V5, P1023 HIROTA T, 2000, J CELL BIOL, V149, P1073 HOOD JK, 2000, BIOCHIM BIOPHYS ACTA, V1471, P31 HOYT MA, 2001, J CELL BIOL, V154, P909 KAITNA S, 2000, CURR BIOL, V10, P1172 KARKI S, 1999, CURR OPIN CELL BIOL, V11, P45 KARKI S, 2002, MOL BIOL CELL, V13, P1722 KRON SJ, 1995, CURR OPIN CELL BIOL, V7, P845 LAW SF, 1996, MOL CELL BIOL, V16, P3327 LAW SF, 2000, MOL CELL BIOL, V20, P5184 LAW SF, 1999, EXP CELL RES, V252, P224 LAW SF, 1998, MOL CELL BIOL, V18, P3540 LEOPOLD P, 1991, CELL, V66, P1207 LEW DJ, 1993, J CELL BIOL, V120, P1305 LEW DJ, 1991, CELL, V66, P1197 0270-7306