Mice lacking a functional CHK gene have no apparent defects in the hematopoietic system

Samokhvalov, Igor M.; Hendrikx, Jan; Visser, J. W. M.; Belyavsky, A. V.; Sotiropolous, Damianos; Gu, Hua

doi:10.1080/15216549700203881

Cited by 11 publications

(13 citation statements)

References 5 publications

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“…Mice lacking the CHK gene have no apparent defects in the hematopoietic system (Samokhvalov et al, 1997). Our results indicate that both anchorage-independent cell growth (colony formation in soft agar) and cell invasion (Matrigel, San Jose, CA, USA) of CHK-overexpressed DLD-1 cells were significantly decreased as compared to control transfected cells (Figure 8).…”

Section: Chk Affects Anchorage-independent Growth and Invasion Of Colsupporting

confidence: 48%

Decreased CHK protein levels are associated with Src activation in colon cancer cells

et al. 2007

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Src activation has been associated with colon cancers but the mechanism underlying Src activation is largely unknown. Csk-homologous kinase (CHK) can inhibit the kinase activity of certain Src kinase family members in vitro by phosphorylating the C-terminal tyrosine and by a non-catalytic mechanism. CHK was previously reported to be expressed primarily in brain and hematopoietic cells. We report herein that CHK is also expressed in normal colon cell lines. Furthermore, CHK protein levels are significantly decreased in various colon cancer cell lines and the decrease correlates with the increased specific activity of Src in these cell lines, while the level of the other Src inhibitory kinase, C-terminal Src kinase, is not significantly changed. CHK is also expressed in normal colon tissues but its expression level is decreased in colon cancer tissues collected from the same patients. Immunofluorescence microscopy shows that CHK colocalizes with Src in normal colon FHC cells. Overexpression of CHK in colon cancer cells results in inactivation of Src without phosphorylating Y530 at its C-terminus. In addition, CHK suppresses anchorage-independent cell growth and cell invasion of colon cancer cells. These results reveal a potentially important role for CHK in Src activation and tumorigenicity in colon cancer cells.

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Section: Chk Affects Anchorage-independent Growth and Invasion Of Colsupporting

confidence: 48%

Decreased CHK protein levels are associated with Src activation in colon cancer cells

et al. 2007

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“…In contrast to Clast3, whose expression is up-regulated upon cell growth, Chk expression is not correlated with cell proliferation (24). Moreover, Chk-deficient cells grow normally (25), whereas Clast3 seems to be required for normal cell cycle progression. These observations suggest that although similar phenotypes are induced by the overexpression of these three divergent proteins, the underlying mechanisms are likely to be different.…”

Section: Discussionmentioning

confidence: 87%

Growth Retardation, Polyploidy, and Multinucleation Induced by Clast3, a Novel Cell Cycle-regulated Protein

Bahar

O-Wang

Kawamura

et al. 2002

Journal of Biological Chemistry

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We have identified a novel gene, Clast3, by subtraction of cDNAs derived from activated and naive B lymphocytes. Clast3 expression is elevated in cycling cells and down-regulated in cells undergoing growth arrest, indicating that its expression is controlled in a cell cycledependent manner. The deduced amino acid sequence of Clast3 cDNA exhibits no significant homology to the known proteins in mammalian and other species. Immunofluorescence staining revealed that Clast3 localizes into discrete nuclear foci. Forced expression of Clast3 results in growth retardation, polyploidy, and generation of multinucleated cells. Treatment of Clast3 transfectants with nocodazole, a spindle-damaging agent, greatly enhances the incidence of the multinucleated cells, suggesting that Clast3 overexpression impairs the same checkpoint activated by nocodazole. Down-regulation of Clast3 expression by antisense oligonucleotides results in a decrease of cells at G 2 -M phase and a concomitant increase of apoptotic cells. These findings indicate that Clast3 is a novel cell cycle-regulated protein and that its constitutive overexpression induces polyploidy and multinucleation by interfering with the mitotic spindle checkpoint.Genetic stability is achieved by the coordinated regulation of DNA replication and repair, chromosomal segregation, and cell cycle checkpoints (1, 2). There are several checkpoints that act to ensure the orderly progression of critical events in the cell cycle. The mitotic spindle checkpoint functions to delay the metaphase to anaphase transition until all pairs of sister chromatids are attached to spindle microtubes, thereby ensuring the correct segregation of duplicated chromosomes into the two daughter cells (3,4). A number of proteins have been identified that sense the kinetochore microtube attachment and regulate the separation of sister chromatids. These include the kinetochore-associated CENPE, MAD, and BUB proteins, the anaphase-promoting complex/cyclosome and its associated cofac-

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“…13 Mice lacking the expression of Matk/CHK have been demonstrated to have no overt phenotype. 5,7 Those earlier studies focused on hematopoietic cells due to the restricted expression of Matk/CHK in these cells. Since then, more lineage markers have been defined, which allow us to supplement the prior hematopoietic cell analyses.…”

Section: Resultsmentioning

confidence: 99%

“…5 Additionally, whereas Csk homozygous mutant embryos exhibit a complex phenotype (including defects in the neural tube) and die between days 9 and 10 of gestation, 6 Matk/CHK knockout mice are fully immunocompetent, have normal peripheral hematopoietic cell populations, a normal life span, and are fertile. 5,7 Despite the restricted expression of MATK/CHK in brain and hematopoietic cells, its role in these cells has not been studied extensively. This is due partly to the absence of an overt phenotype in the Matk/CHK knockout (KO, Ϫ/Ϫ) mice.…”

Section: Introductionmentioning

confidence: 99%

“…This is due partly to the absence of an overt phenotype in the Matk/CHK knockout (KO, Ϫ/Ϫ) mice. 5,7 Here, we redefined the role of MATK/CHK using Matk/CHK Ϫ/Ϫ mice. Whereas Matk/CHK Ϫ/Ϫ mice appear to be normal in the steady state, stimulation of the hematopoietic cells of these mice with IL-7 and in vivo challenge with antigen (TNP-ovalbumin [TNP-Ova]) led to strikingly different physiologic responses, compared with the similarly treated hematopoietic cells of the Matk/CHK ϩ/ϩ mice.…”

Section: Introductionmentioning

confidence: 99%

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Identification of the nonreceptor tyrosine kinase MATK/CHK as an essential regulator of immune cells using Matk/CHK-deficient mice

Lee

Avraham

Imamoto

et al. 2006

Blood

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Mice lacking a functional CHK gene have no apparent defects in the hematopoietic system

Cited by 11 publications

References 5 publications

Decreased CHK protein levels are associated with Src activation in colon cancer cells

Decreased CHK protein levels are associated with Src activation in colon cancer cells

Growth Retardation, Polyploidy, and Multinucleation Induced by Clast3, a Novel Cell Cycle-regulated Protein

Identification of the nonreceptor tyrosine kinase MATK/CHK as an essential regulator of immune cells using Matk/CHK-deficient mice

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