Structure, Expression, and Chromosomal Localization of Human GAK

Kimura, Shinya; Tsuruga, Hifumi; Yabuta, Norikazu; Endo, Yuichi; Nishimura, Hiroshi

doi:10.1006/geno.1997.4873

Cited by 59 publications

(56 citation statements)

References 28 publications

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“…The homozygous cyclin G1 7/7 mice were indistinguishable from their wild-type and heterozygous (cyclin G1 +/7 ) littermates. Pathological analyses of cyclin G1 +/+ and cyclin G1 7/7 mice revealed no obvious di erence between mutant and wild-type mice at 2, 6 or 8 weeks of age in skeletal muscle, heart, kidney, brain or testis; cyclin G1 mRNA is strongly expressed in all of these tissues (Kimura et al, 1997b). There were also no di erences in 14-day whole embryos or in other tissues including cerebrum, cerebellum, heart, lung, skeletal muscle, spine, bone marrow, skin, lymph node, testis, stomach, intestine, liver, kidney and at 2, 6, or 8 weeks of age (data not shown).…”

Section: Targeted Disruption Of Cyclin G1 Genementioning

confidence: 94%

“…Total cellular protein was prepared as described previously (Kimura et al, 1997b), resolved by SDS-polyacrylamide gel electrophoresis (SDS ± PAGE) on 10% gels, transferred to nitrocellulose ®lters and probed with anti-cyclin G1 polyclonal antibody (PAb) (Kimura et al, unpublished), anticyclin G2 polyclonal antibody (PAb) (Kimura et al, unpublished) or anti-cdk 2 monoclonal antibody (clone 8A12; MBL, Nagoya, Japan). Immunoreactive protein bands were visualized using Renaissense TM chemiluminescence reagents (DuPont NEN, Boston MA, USA).…”

Section: Western Blot Analysesmentioning

confidence: 99%

“…In the course of searching for proteins which associate with cyclin G1, we have demonstrated the association of cyclin G1 with cdk5 in vivo and isolated another association partner, a non-cdk serine/threonine kinase named GAK (Kanoka et al, 1997;Kimura et al, 1997b). Others have reported a p53-dependent association between cyclin G1 and the B' regulatory subunit of protein phosphatase 2A (Okamoto et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Cyclin G1 is involved in G2/M arrest in response to DNA damage and in growth control after damage recovery

et al. 2001

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Cyclin G1 is one of the target genes of the transcription factor p53, and is induced in a p53-dependent manner in response to DNA damage. Although cyclin G1 has been implicated in a range of biological phenomena, its precise function remains unclear. Here we present an analysis of the physiological role of cyclin G1 using mice homozygous for a targeted disruption of the cyclin G1 gene. In order to clarify the role of cyclin G1 in the p53 pathway, downstream events such as apoptosis, cell growth and cell cycle checkpoint control were analysed in thymocytes and embryonic ®broblasts derived from cyclin G1-disrupted mice. No di erence was detected in induction of apoptosis between mouse embryo ®broblasts (MEFs) derived from cyclin G1 +/+ and cyclin G1 7/7 mice. Following irradiation, cyclin G1 7/7 MEFs proliferated more slowly and reached lower cell densities in culture dishes than cyclin G1 +/+ MEFs. Analysis of cell survival showed that cyclin G1 7/7 MEFs were about twice as sensitive as cyclin G1 +/+ MEFs to g radiation or UV radiation. Cyclin G1 7/7 mice were more sensitive to g radiation than wild-type mice. Flow cytometeric analysis revealed that the number of cyclin G1 7/7 MEFs in G2/ M phase after irradiation was reduced by 50% relative to cyclin G1 +/+ MEFs. Our results demonstrate that cyclin G1 plays roles in G2/M arrest, damage recovery and growth promotion after cellular stress. Oncogene (2001) 20, 3290 ± 3300.

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Section: Targeted Disruption Of Cyclin G1 Genementioning

confidence: 94%

Section: Western Blot Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cyclin G1 is involved in G2/M arrest in response to DNA damage and in growth control after damage recovery

et al. 2001

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“…26 Cyclin A/CDK2-associated protein P19 (AA136533) and p45 form a complex with cyclin A/CDK2, and the activity of this complex is essential for S phase. 27 Cyclin-G-associated kinase GAK (AA428959), whose expression is somewhat oscillatory and peaks in G1, 28 associates with CDK5.…”

Section: Cell Cycle Regulationmentioning

confidence: 99%

Stimulation-induced gene expression in Ramos B-cells

Ollila

Vihinen

2003

Genes Immun

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The development of adaptive immunity and responses to foreign molecules and organisms relies on the highly regulated production of hundreds of proteins. B-cell maturation, from committed progenitors to terminally differentiated plasma cells, is a multistep process that requires the ordered expression of a large number of genes. We studied anti-IgM-stimulated Ramos cells to explore genome-wide expression patterns in differentiating human B-cells. cDNA microarrays were used to measure changes in transcript levels over several days. A large set of genes (B1500) showed significantly altered expression at one or more time points. The expression profiles were used to construct gene clusters that were then characterized further with respect to the functions of the encoded proteins. Several groups of genes relevant to B-cells were analyzed in detail including early response genes and genes related to transcription, apoptosis and cell cycle regulation. Extensive bioinformatics analyses were conducted to identify the genes/proteins and to study functions and pathways involving B-cells. The results pave the way for understanding the development of humoral immunity, and provide new candidate genes and targets for research and drug development.

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“…Cyclin G1 is associated with cyclin-dependent kinase 5 (CDK5) and non-CDK-serine/ threonin kinase, named cyclin G associated kinase (GAK). 3,4 In addition, cyclin G1 has been suggested to act as an oncogenic protein, because of its overexpression in human tumor cells. 5,6 On the other hand, cyclin G is also involved in G2/M arrest in response to DNA damage 7 or in the facilitation of TNF-induced apoptosis, 8 implicating tumor suppressive function.…”

Section: Introductionmentioning

confidence: 99%

Cyclin G1 overcomes radiation-induced G2 arrest and increases cell death through transcriptional activation of cyclin B1

Seo

Lee

et al. 2005

Cell Death Differ

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Although cyclin G1 has been implicated in certain p53-related biological phenomena, other aspects of its function remain unclear. Here we report hitherto unknown mechanism by which cyclin G1 increases radiation sensitivity by regulating the level of cyclin B1. Overexpression of cyclin G1 was observable in lung carcinoma tissues. Irradiation of human lung cells with cyclin G1 overexpression resulted in increased cell death and c-H2AX foci suggesting that cyclin G1 rendered the cells more susceptible to DNA damage. Enhanced radiosensitivity by cyclin G1 was correlated with increased cyclin B1, CDC2/cyclin B1 complex, and MPM2. Cell cycle synchronization clearly showed coexpression of cyclin G1 and cyclin B1 in G2/M phase. Depletion of cyclin G1 by interference RNA revealed that cyclin G1 regulated transcription of cyclin B1 in a p53-independent manner, and confirmed that the increased mitotic cells and cell death by cyclin G1 were dependent upon cyclin B1. Therefore, our data suggest that cyclin G1 enhanced radiation sensitivity by overriding radiation-induced G2 arrest through transcriptional upregulation of cyclin B1.

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Structure, Expression, and Chromosomal Localization of Human GAK

Cited by 59 publications

References 28 publications

Cyclin G1 is involved in G2/M arrest in response to DNA damage and in growth control after damage recovery

Cyclin G1 is involved in G2/M arrest in response to DNA damage and in growth control after damage recovery

Stimulation-induced gene expression in Ramos B-cells

Cyclin G1 overcomes radiation-induced G2 arrest and increases cell death through transcriptional activation of cyclin B1

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