Increased expression of a 58-kDa protein kinase leads to changes in the CHO cell cycle.

Bunnell, Bruce A.; Heath, Lucie S.; Adams, Donald E.; Lahti, Jill M.; Kidd, Vincent J.

doi:10.1073/pnas.87.19.7467

Cited by 141 publications

(115 citation statements)

References 30 publications

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“…However, ectopic expression of a p50 mutant PITSLRE kinase resembling the cleaved form of p110 induces apoptosis. 44 (iv) Tripping up the competition III: regulation of components of the cell death receptor machinery Two kinases identified as components of the cell death machinery, RIPK1 and fyn, are caspase substrates. The protein kinase fyn associates directly with the TCR and with Fas.…”

Section: (I) Kinases That Regulate Cell Morphologymentioning

confidence: 99%

Life and death decisions: regulation of apoptosis by proteolysis of signaling molecules

2000

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Caspases are the major executioners of cell death, serving as molecular guillotines to behead many proteins required for maintenance of cellular homeostasis. Identification of caspase substrates has taken on increasing importance as we attempt to better understand the molecular mechanisms involved in regulating the struggle between life and death. Many caspase substrates have been described and include RNA binding proteins such as La and U1-70 kD, structural proteins such as keratin and nuclear lamins, and transcription factors or their regulatory proteins that include IkB, SP1, and SREBP. Kinases and other signaling proteins are perfectly suited to regulate life and death decisions in response to cellular stressors and have only recently been identified as important caspase substrates. Here we review the current status of signaling pathways that are activated, inactivated or dysregulated by proteases such as caspases and calpain to control entry into apoptosis. The emerging concept that some caspase pathways may be inhibited by cellular and viral apoptosis inhibitory proteins while other caspase pathways are preserved suggests that a subset of these kinases may exist as cleaved`isoforms' in cells that are not destined to perish. By acting as executioners and as important`molecular sensors' of the degree of cellular injury, the signaling proteins described in this review are strong candidates to mediate downstream events, both in condemned and in viable cells.

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Section: (I) Kinases That Regulate Cell Morphologymentioning

confidence: 99%

Life and death decisions: regulation of apoptosis by proteolysis of signaling molecules

2000

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“…Furthermore, a number of protein kinases have been identified as caspase substrates, and their processing by these proteases frequently generates active forms of these kinases by removing autoinhibitory domains (4 -12). Ectopic expression of these activated protein kinases induces many of the biochemical and cellular changes associated with cell death, suggesting that they participate in regulating some aspect of apoptotic signaling (9,10,(13)(14)(15). Based on these studies, it is tempting to speculate that caspase cleavage and activation of specific protein kinases/phosphatases during apoptosis facilitate caspase processing of certain protein targets.…”

mentioning

confidence: 99%

“…The larger PITSLRE p110 isoforms may function to regulate some aspect of RNA splicing/transcription during the cell cycle (19), and they are cleaved by caspase-1 and caspase-3 during TNF␣ 1 -induced cell death (20). In addition, ectopic expression of a PITSLRE p50 isoform that resembles the final caspase-modified product has been shown to induce apoptosis (13). Fas-mediated T-cell death has also been correlated with PITSLRE proteolysis and an increase in its histone H1 kinase activity (4).…”

mentioning

confidence: 99%

Phosphorylation of PITSLRE p110 Isoforms Accompanies Their Processing by Caspases during Fas-mediated Cell Death

Tang

Gururajan

Kidd

1998

Journal of Biological Chemistry

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A number of cellular proteins have been identified as caspase targets during cell death, including the PITSLRE protein kinases. These targets generally fall into one of three possible categories: 1) other caspases, 2) proteins that are inactivated during apoptosis, and 3) proteins that are required for execution of the cell death program. However, not all proteins are cleaved by caspases during apoptosis. Why only specific proteins are destined to be processed by caspases during cell death is currently not clear. Here we show that multiple caspase-like activities are involved in the processing of the PITSLRE p110 isoforms during Fas-induced apoptosis in Jurkat T-cells. Three p110 caspase cleavage sites have been mapped to the amino-terminal domain of p110 and verified by site-directed mutagenesis. Curiously, the mutagenesis studies revealed that cleavage of two juxtaposed caspase sites is necessary for the complete processing of this protein during cell death in vivo. Finally, we demonstrate that the PITSLRE p110 protein is rapidly phosphorylated during Fas-induced apoptosis in Jurkat cells and that phosphorylation of an aminoterminal portion of the protein may enhance caspase cleavage in this region.

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“…The PITSLRE homologues exist in human, mouse, chicken, Drosophila, and Xenopus, suggesting that their functions may be well conserved (16,19,26,27). The small p58 PITSLRE isoform was originally isolated from a human liver cDNA library and has a 299-amino acid region with 68% homology to the p34 cdc2 protein kinase (16).…”

mentioning

confidence: 99%

“…The p110 PITSLRE isoform can be detected in all phases of the cell cycle, whereas the p58 PITSLRE is mainly expressed in G 2 /M phase (28). Ectopic expression of p58 PITSLRE in Chinese hamster ovary fibroblasts leads to a late telophase delay, abnormal cytokinesis, and a reduced rate of cell growth (16). Conversely, the diminished expression of p58 PITSLRE mRNA is found to increase DNA replication and enhance cell growth (17).…”

mentioning

confidence: 99%

Interaction of p58PITSLRE, a G2/M-specific Protein Kinase, with Cyclin D3

Zhang¹,

Cai²,

Zhang

et al. 2002

Journal of Biological Chemistry

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The p58PITSLRE is a p34 cdc2 -related protein kinase that plays an important role in normal cell cycle progression. Elevated expression of p58 PITSLRE in eukaryotic cells prevents them from undergoing normal cytokinesis and appears to delay them in late telophase. To investigate the molecular mechanism of p58 PITSLRE action, we used the yeast two-hybrid system, screened a human fetal liver cDNA library, and identified cyclin D3 as an interacting partner of p58 PITSLRE . In vitro binding assay, in vivo coimmunoprecipitation, and immunofluorescence cell staining further confirmed the association of p58 PITSLRE with cyclin D3. This binding was observed only in the G 2 /M phase but not in the G 1 /S phase of the cell cycle; meanwhile, no interaction between p110 PITSLRE and cyclin D3 was observed in all the cell cycle. The overexpression of cyclin D3 in 7721 cells leads to an exclusively accumulation of p58 PITSLRE in the nuclear region, affecting its cellular distribution. Histone H1 kinase activity of p58 PITSLRE was greatly enhanced upon interaction with cyclin D3. Furthermore, kinase activity of p58 PITSLRE was found to increase greatly in the presence of cyclin D3 using a specific substrate, ␤-1,4-galactosyltransferase 1. These data provide a new clue to our understanding of the cellular function of p58 PITSLRE and cyclin D3.

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Increased expression of a 58-kDa protein kinase leads to changes in the CHO cell cycle.

Cited by 141 publications

References 30 publications

Life and death decisions: regulation of apoptosis by proteolysis of signaling molecules

Life and death decisions: regulation of apoptosis by proteolysis of signaling molecules

Phosphorylation of PITSLRE p110 Isoforms Accompanies Their Processing by Caspases during Fas-mediated Cell Death

Interaction of p58PITSLRE, a G2/M-specific Protein Kinase, with Cyclin D3

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