Dynamic changes of NuMA during the cell cycle and possible appearance of a truncated form of NuMA during apoptosis

1996 ◽  
Vol 109 (2) ◽  
pp. 277-288 ◽  
Author(s):  
H.L. Hsu ◽  
N.H. Yeh
Keyword(s):  
Cell Cycle ◽  
Hela Cells ◽  
Structural Integrity ◽  
Chromatin Condensation ◽  
Tail Domain ◽  
Truncated Form ◽  
Cdc2 Kinase ◽  
Mitotic Apparatus ◽  
Interphase Cells ◽  
Late Stages

We have demonstrated that dynamic redistribution of nuclear-mitotic apparatus (NuMA) protein in the cell cycle is correlated temporally and spatially with its biochemical modifications. In interphase, NuMA behaves solely as a 220 kDa nuclear matrix-associated protein. After initiation of DNA condensation during mitosis, NuMA is phosphorylated by Cdc2 kinase into a 240 kDa form which is transported quickly to the centrosomal region. Once cells have passed the metaphase-anaphase transition, the 240 kDa form of NuMA either becomes a 180 kDa truncated form which is fated to be degraded completely before mitotic exit, or returns to the 220 kDa form that relocates to the daughter nuclei and remains throughout interphase. Apparently, a proteolytic enzyme is activated during the late stages of mitosis. After induction of a 180 kDa form of NuMA in interphase HeLa cells by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, nuclear apoptotic phenomena including chromatin condensation, DNA fragmentation, and micronucleation were observed. However, the same treatment did not induce apoptosis in mitotic phase-arrested HeLa cells. The 180 kDa form of NuMA was demonstrated to be a truncated product, at least lacking the tail domain. When HL60 cells were stimulated by diverse apoptosis inducers such as camptothecin, staurosporine, cycloheximide, and A23187, the extent of NuMA cleavage to produce a 180 kDa product was comparable with the degree of oligonucleosomal laddering. NuMA cleavage is likely to be a consequence of the onset of apoptosis. The intact 220 kDa NuMA functions in interphase cells to retain the nuclear structural integrity. Additionally, NuMA appears to act as a nuclear structural target for a death protease during apoptosis.

Changes in the organization of chromosomes during the cell cycle: response to ultraviolet light

1975 ◽  
Vol 17 (3) ◽  
pp. 539-565
Author(s):  
S.L. Schor ◽  
R.T. Johnson ◽  
C.A. Waldren
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Ultraviolet Light ◽  
Hela Cells ◽  
Close Correlation ◽  
Chromosome Condensation ◽  
Unscheduled Dna Synthesis ◽  
Interphase Chromosome ◽  
Interphase Cells ◽  
Chromosome Decondensation

Fusion between mitotic and interphase cells results in the premature condensation of the interphase chromosomes into a morphology related to the position in the cell cycle at the time of fusion. These prematurely condensed chromosomes (PCC) have been used in conjunction with u.v. irradiation to examine the interphase chromosome condensation cycle of HeLa cells. The following observations have been made: (I) There is a progressive decondensation of the chromosomes during G1 which is accentuated by u.v. irradiation: (2) The chromosomes become more resistant to u.v.-induced decondensation during G2 and mitosis. (3) There is a close correlation between the degree of chromosome decondensation and the amount of unscheduled DNA synthesis induced by u.v. irradiation during G1 and mitosis: (4) Hydroxyurea enhances the ability of u.v. irradiation to promote the decondensation of chromosomes during G1, G2 and mitosis. Hydroxyurea also potentiates the lethal action of u.v. irradiation during mitosis and G1. These data are discussed in relation to the suggestion that chromosomes undergo a progressive decondensation during G1 and condensation during G2.

MSA-35: a protein identified by human autoantibodies that colocalizes with microtubules

1992 ◽  
Vol 70 (10-11) ◽  
pp. 1115-1122 ◽  
Author(s):  
J. B. Rattner ◽  
T. Wang ◽  
G. Mack ◽  
L. Martin ◽  
M. J. Fritzler
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Hela Cells ◽  
Temporal Distribution ◽  
Mitotic Arrest ◽  
Spatial And Temporal Distribution ◽  
Intercellular Bridge ◽  
Centrosome Separation ◽  
Interphase Cells ◽  
Low Levels

We have identified a putative 35-kilodalton protein that colocalizes with microtubules and displays a unique spatial and temporal distribution during the cell cycle of HeLa cells. This protein has been given the designation MSA-35. MSA-35 first appears in association with microtubules and centrosomes of interphase cells exhibiting centrosome separation as a prelude to cell division. This protein is found in conjunction with kinetochore microtubules throughout their appearance. MSA-35 transiently associates with interpolar microtubules following anaphase and the pattern of MSA-35 reactivity in telophase cells suggests that there are at least seven domains within the intercellular bridge. The distribution of MSA-35 during and following recovery from mitotic arrest with nocodazole suggest that it is also present at low levels in interphase cells, can associate with interphase centrosomes, and colocalizes with nascent microtubules. The complex spatial and temporal distribution of MSA-35 indicates that it may be necessary for a series of events in the mitotic process such as the bundling of microtubules.Key words: mitosis, autoantibodies, spindle.

MAP4 Is the in Vivo Substrate for CDC2 Kinase in HeLa Cells:  Identification of an M-Phase Specific and a Cell Cycle-Independent Phosphorylation Site in MAP4†

Biochemistry ◽  
1997 ◽  
Vol 36 (50) ◽  
pp. 15873-15883 ◽  
Author(s):  
Kayoko Ookata ◽  
Shin-ichi Hisanaga ◽  
Minoru Sugita ◽  
Akira Okuyama ◽  
Hiromu Murofushi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Hela Cells ◽  
Phosphorylation Site ◽  
Cdc2 Kinase ◽  
M Phase ◽  
A Cell

scholarly journals Mitotic cytosol inhibits invagination of coated pits in broken mitotic cells.

1991 ◽  
Vol 114 (6) ◽  
pp. 1159-1166 ◽  
Author(s):  
M Pypaert ◽  
D Mundy ◽  
E Souter ◽  
J C Labbé ◽  
G Warren
Keyword(s):  
Liquid Nitrogen ◽  
Okadaic Acid ◽  
Hela Cells ◽  
Mammalian Cells ◽  
A431 Cells ◽  
Coated Pits ◽  
Cdc2 Kinase ◽  
Phosphatase Inhibitor ◽  
Interphase Cells ◽  
Mitotic Cells

Receptor-mediated endocytosis is inhibited during mitosis in mammalian cells and earlier work on A431 cells suggested that one of the sites inhibited was the invagination of coated pits (Pypaert, M., J. M. Lucocq, and G. Warren. 1987. Eur. J. Cell Biol. 45: 23-29). To explore this inhibition further, we have reproduced it in broken HeLa cells. Mitotic or interphase cells were broken by freeze-thawing in liquid nitrogen and warmed in the presence of mitotic or interphase cytosol. Using a morphological assay, we found invagination to be inhibited only when mitotic cells were incubated in mitotic cytosol. This inhibition was reversed by diluting the cytosol during the incubation. Reversal was sensitive to okadaic acid, a potent phosphatase inhibitor, showing that phosphorylation was involved in the inhibition of invagination. This was confirmed using purified cdc2 kinase which alone could partially substitute for mitotic cytosol.

scholarly journals Campylobacter jejuni Cytolethal Distending Toxin Causes a G2-Phase Cell Cycle Block

1998 ◽  
Vol 66 (5) ◽  
pp. 1934-1940 ◽  
Author(s):  
Chris A. Whitehouse ◽  
Paul B. Balbo ◽  
Everett C. Pesci ◽  
Daniel L. Cottle ◽  
Peter M. Mirabito ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Campylobacter Jejuni ◽  
Hela Cells ◽  
Chromatin Condensation ◽  
Phase Cell ◽  
Specific Cell ◽  
Cytolethal Distending Toxin ◽  
Cycle Arrest ◽  
M Phase

ABSTRACT Cytolethal distending toxin (CDT) from the diarrheagenic bacteriumCampylobacter jejuni was shown to cause a rapid and specific cell cycle arrest in HeLa and Caco-2 cells. Within 24 h of treatment, CDT caused HeLa cells to arrest with a 4N DNA content, indicative of cells in G2 or early M phase. Immunofluorescence studies indicated that the arrested cells had not entered M phase, since no evidence of tubulin reorganization or chromatin condensation was visible. CDT treatment was also shown to cause HeLa cells to accumulate the inactive, tyrosine-phosphorylated form of CDC2. These results indicated that CDT treatment results in a failure to activate CDC2, which leads to cell cycle arrest in G2. This mechanism of action is novel for a bacterial toxin and provides a model for the generation of diarrheal disease byC. jejuni and other diarrheagenic bacteria that produce CDT.

PTTG has a Dual Role of Promotion-Inhibition in the Development of Pituitary Adenomas

2019 ◽  
Vol 26 (11) ◽  
pp. 800-818
Author(s):  
Zujian Xiong ◽  
Xuejun Li ◽  
Qi Yang
Keyword(s):  
Cell Cycle ◽  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Cell Cycle Progression ◽  
Key Factors ◽  
Cycle Progression ◽  
Sister Chromatids ◽  
Regulation Of Cell Cycle ◽  
Late Stages

Pituitary Tumor Transforming Gene (PTTG) of human is known as a checkpoint gene in the middle and late stages of mitosis, and is also a proto-oncogene that promotes cell cycle progression. In the nucleus, PTTG works as securin in controlling the mid-term segregation of sister chromatids. Overexpression of PTTG, entering the nucleus with the help of PBF in pituitary adenomas, participates in the regulation of cell cycle, interferes with DNA repair, induces genetic instability, transactivates FGF-2 and VEGF and promotes angiogenesis and tumor invasion. Simultaneously, overexpression of PTTG induces tumor cell senescence through the DNA damage pathway, making pituitary adenoma possessing the potential self-limiting ability. To elucidate the mechanism of PTTG in the regulation of pituitary adenomas, we focus on both the positive and negative function of PTTG and find out key factors interacted with PTTG in pituitary adenomas. Furthermore, we discuss other possible mechanisms correlate with PTTG in pituitary adenoma initiation and development and the potential value of PTTG in clinical treatment.

Centrosome Structure And Function Is Altered By Experimental Manipulations With Formamide: Implications For Abnormal Cell Divisions During Cancer

1999 ◽  
Vol 5 (S2) ◽  
pp. 1286-1287
Author(s):  
Heide Schatten ◽  
Christopher N. Hueser ◽  
Amitabha Chakrabarti
Keyword(s):  
Cell Cycle ◽  
Genomic Stability ◽  
Cellular Regulation ◽  
Mitotic Apparatus ◽  
Abnormal Cell ◽  
Chemical Agents ◽  
Abnormal Mitosis ◽  
And Function ◽  
Normal Mitosis ◽  
Abnormal Cell Proliferation

The formation of abnormal mitosis associated with cancer has been intriguing for many decades. While microtubules had been the focus of previous studies, recent research has focused on centrosomes, microtubule organizing centers which organize the mitotic apparatus during cell division. During normal mitosis centrosomes form two poles but in cancer, centrosomes can form three, four, or more poles, and organize tripolar, quadripolar, and multipolar mitoses, respectively. This has severe consequences for genomic stability because chromosomes are separated unequally to three, four, or more poles. This can result in aneuploidy and gene amplifications with multiple defects in cellular regulation. It can result in malignancy that is accompanied by cell cycle imbalances and abnormal cell proliferation. While radiation and chemical agents are known to damage DNA and can lead to cell cycle abnormalities, the damage of centrosome structure leading to abnormal mitosis deserves also consideration.

scholarly journals Phosphorylation of neurofilament H subunit at the tail domain by CDC2 kinase dissociates the association to microtubules.

1991 ◽  
Vol 266 (32) ◽  
pp. 21798-21803 ◽  
Author(s):  
S. Hisanaga ◽  
M. Kusubata ◽  
E. Okumura ◽  
T. Kishimoto
Keyword(s):  
Tail Domain ◽  
Cdc2 Kinase

scholarly journals Slm9, a Novel Nuclear Protein Involved in Mitotic Control in Fission Yeast

Genetics ◽  
2000 ◽  
Vol 155 (2) ◽  
pp. 623-631
Author(s):  
Junko Kanoh ◽  
Paul Russell
Keyword(s):  
Cell Cycle ◽  
Fission Yeast ◽  
Cell Elongation ◽  
Nuclear Protein ◽  
G1 Arrest ◽  
Permissive Temperature ◽  
Cdc2 Kinase ◽  
Synthetic Lethal ◽  
Cycle Arrest ◽  
Novel Protein

Abstract In the fission yeast Schizosaccharomyces pombe, as in other eukaryotic cells, Cdc2/cyclin B complex is the key regulator of mitosis. Perhaps the most important regulation of Cdc2 is the inhibitory phosphorylation of tyrosine-15 that is catalyzed by Wee1 and Mik1. Cdc25 and Pyp3 phosphatases dephosphorylate tyrosine-15 and activate Cdc2. To isolate novel activators of Cdc2 kinase, we screened synthetic lethal mutants in a cdc25-22 background at the permissive temperature (25°). One of the genes, slm9, encodes a novel protein of 807 amino acids. Slm9 is most similar to Hir2, the histone gene regulator in budding yeast. Slm9 protein level is constant and Slm9 is localized to the nucleus throughout the cell cycle. The slm9 disruptant is delayed at the G2-M transition as indicated by cell elongation and analysis of DNA content. Inactivation of Wee1 fully suppressed the cell elongation phenotype caused by the slm9 mutation. The slm9 mutant is defective in recovery from G1 arrest after nitrogen starvation. The slm9 mutant is also UV sensitive, showing a defect in recovery from the cell cycle arrest after UV irradiation.

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