Cyclin A1, the alternative A-type cyclin, contributes to G1/S cell cycle progression in somatic cells

Ji, Ping; Agrawal, Shuchi; Diederichs, Sven; Bäumer, Nicole; Becker, Annette; Cauvet, Thomas; Kowski, Sascha; Beger, Carmela; Welte, Karl; Berdel, Wolfgang E.; Serve, Hubert; Müller‐Tidow, Carsten

doi:10.1038/sj.onc.1208356

Cited by 89 publications

(80 citation statements)

References 22 publications

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“…Leukemic U937 cells were retrovirally transduced with cyclin A1, and cyclin A1 overexpression was confirmed both on the mRNA and protein level. 27 Consistent with upregulation of cyclin A1 and cyclin A1/CDK2 kinase activity (Figs. 1a and 1b), the phosphorylation of RB was significantly increased (Fig.…”

Section: Rb Phosphorylation Correlates With Cyclin A1 Expression In Lmentioning

confidence: 48%

“…26 Cyclin A1 contributes to G1 to S cell cycle progression in somatic cells. 27 In the current study, we provide evidence for a molecular switch in A-type cyclin activity towards cyclin A1, which inhibits apoptosis by modulating RB functions; accelerates DNA double strand break repair by altering Ku70 binding activity in leukemia cells. …”

mentioning

confidence: 90%

“…27 However, the roles of the different A-type cyclins in leukemic cells remain unclear. Since the G1/S transition is regulated by the RB/E2F pathway, we examined the connections between cyclin A1 and the RB/E2F pathway in vivo.…”

Section: Rb Phosphorylation Correlates With Cyclin A1 Expression In Lmentioning

confidence: 99%

“…27 Briefly, human cyclin A1 cDNA was cloned into the pLXIN vector. Retroviral supernatant was generated after transfection of either pLXIN-cyclin A1 or pLXIN empty vector into the 293T cells with gag-pol and VSV-G. U937 cells were retrovirally transduced.…”

Section: Overexpression Of Cyclin A1 In Leukemic U937 Cellsmentioning

confidence: 99%

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DNA damage response involves modulation of Ku70 and Rb functions by cyclin A1 in leukemia cells

Bäumer

Yin

et al. 2007

Intl Journal of Cancer

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Cyclin A1 plays a critical role in hematopoietic malignancies, notably, acute myeloid leukemia. The molecular mechanisms of cyclin A1 action are incompletely understood. Here, we show that cyclin A1 functions are mediated by the retinoblastoma and the Ku70 pathway. High levels of cyclin A1 and the associated CDK2 kinase activity were associated with increasing levels of phosphorylated retinoblastoma in vivo. UV irradiation induced a switch of the CDK2 towards cyclin A1, with accordance to changes in CDK2 kinase activity. The C-terminus of cyclin A1 directly interacted with Ku70, and DNA binding activity of Ku70 was modulated by cyclin A1/ CDK2 and phosphatase treatment. Cyclin A1-deficiency induced by shRNA increased apoptosis that is induced by DNA damage and death receptor ligands. Taken together, these analyses demonstrate that cyclin A1 exerts antiapoptotic functions by interacting with retinoblastoma and Ku proteins in leukemia cells. ' 2007 Wiley-Liss, Inc.Key words: cyclin A1; cell cycle control; DNA repair; apoptosis Cell cycle dysregulation is one of the key phenomena in the pathogenesis of cancer. Cyclins and cyclin-dependent kinases (CDKs) are essential components for cell cycle control and development in eukaryotes. An important concept is that cyclin D-CDK4/CDK6 phosphorylate Rb. Hyperphosphorylation by cyclin E/CDK2 or cyclin E/CDK1 at additional sites releases E2F from E2F/RB complexes and allows transcriptional activation of cell cycle progression genes. 1-4 CDK2/cyclin A2 complexes actively regulate DNA replication. 5,6 Aberration of cyclin/CDK activity is commonly associated with tumor formation. [7][8][9][10] Genomic instability is another key feature of tumorigenesis. Mammalian cells have developed a number of repair systems to combat DNA damage and to maintain genomic integrity. 11 Double-strand breaks (DSBs) are the most severe types of DNA lesions. These DSBs are induced by endogenous and exogenous factors, including exposure to ionizing radiation (IR) and radiomimetic drugs, collapse of replication forks and programmed cleavage by specific endonucleases during meiotic recombination and V(D)J recombination. [12][13][14][15] DSBs are potent triggers of cell cycle arrest and apoptosis. 14,16 The effective and accurate regulation of DNA DSB repairs is essential for genomic integrity. Double strand breaks are especially dangerous during S phase when single stranded DNA molecules are processed.Recently, we discovered an important link between cell cycle regulation and DNA DSB repair. 17 DSBs repair can be modulated by A-type cyclins and especially cyclin A1, an alternative A-type cyclin. It is highly expressed in the testis and it plays an important role in spermatogenesis. 18,19 Male mice with cyclin A1 deletion are sterile due to cell cycle arrest and enhanced apoptosis. 20 More recent data suggest that cyclin A1 acts as a dose-dependent regulator of the successful production of haploid cells. 21 In addition to testicular expression, high levels of cyclin A1 have been found in several leukem...

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Section: Rb Phosphorylation Correlates With Cyclin A1 Expression In Lmentioning

confidence: 48%

mentioning

confidence: 90%

Section: Rb Phosphorylation Correlates With Cyclin A1 Expression In Lmentioning

confidence: 99%

Section: Overexpression Of Cyclin A1 In Leukemic U937 Cellsmentioning

confidence: 99%

See 2 more Smart Citations

DNA damage response involves modulation of Ku70 and Rb functions by cyclin A1 in leukemia cells

Bäumer

Yin

et al. 2007

Intl Journal of Cancer

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“…Cell cycle analyses were performed as described using propidium iodide staining or BrdU incorporation combined with propidium iodide staining (39) and subsequent FACS analysis. If indicated, half of the cells were used for RT-PCR to determine Inca1 expression.…”

Section: Methodsmentioning

confidence: 99%

Inhibitor of Cyclin-dependent Kinase (CDK) Interacting with Cyclin A1 (INCA1) Regulates Proliferation and Is Repressed by Oncogenic Signaling

Bäumer

Tickenbrock

Tschanter

et al. 2011

Journal of Biological Chemistry

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The cell cycle is driven by the kinase activity of cyclin⅐cyclin-dependent kinase (CDK) complexes, which is negatively regulated by CDK inhibitor proteins. Recently, we identified INCA1 as an interaction partner and a substrate of cyclin A1 in complex with CDK2. On a functional level, we identified a novel cyclin-binding site in the INCA1 protein. INCA1 inhibited CDK2 activity and cell proliferation. The inhibitory effects depended on the cyclin-interacting domain. Mitogenic and oncogenic signals suppressed INCA1 expression, whereas it was induced by cell cycle arrest. We established a deletional mouse model that showed increased CDK2 activity in spleen with altered spleen architecture in Inca1 ؊/؊ mice. Inca1 ؊/؊ embryonic fibroblasts showed an increase in the fraction of S-phase cells. Furthermore, blasts from acute lymphoid leukemia and acute myeloid leukemia patients expressed significantly reduced INCA1 levels highlighting its relevance for growth control in vivo. Taken together, this study identifies a novel CDK inhibitor with reduced expression in acute myeloid and lymphoid leukemia. The molecular events that control the cell cycle occur in a sequential process to ensure a tight regulation, which is important for the survival of a cell and includes the detection and repair of genetic damage and the prevention of uncontrolled cell division.

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Nano‐Titanium Oxide‐Coated Carbon Nanotubes for Photothermal Therapy in the Treatment of Colorectal Cancer

Xie,

Li,

Niu

et al. 2024

Adv Healthcare Materials

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Carbon nanotubes (CNTs) display good potential in tumor photothermal therapy (PTT). In this study, it is aimed to investigate the therapeutic potential of nano‐titanium oxide‐coated multi‐walled carbon nanotubes (MCNTs) against colorectal cancer (CRC). First, TiO2 nanosheets are modified on the surface of MCNTs to obtain nano‐TiO2‐coated MCNTs. Next, cell compatibility validation is conducted on nano‐TiO2‐coated MCNTs, and it is found that nano‐TiO2‐coated MCNTs are safe within a certain concentration range (0–200 µg mL⁻1). Interestingly, nano‐TiO2‐coated MCNTs display a good killing effect in CRC cells under near‐infrared (NIR) laser irradiation. Subsequently, nano‐TiO2‐coated MCNTs markedly promote the proapoptotic effects of NIR laser irradiation and significantly inhibit the expression of cell cycle proteins CCNA1 and CCND1 in CRC cells under NIR laser irradiation, which indicates that nano‐TiO2‐coated MCNTs exert anti‐CRC effects under NIR laser irradiation by regulating cell apoptosis and cell cycle. Furthermore, nano‐TiO2‐coated MCNTs accelerate inhibitory effects on the AKT signaling pathway under NIR laser irradiation. Finally, a cell line‐derived xenograft model is established, and the results showed that nano‐TiO2‐coated MCNTs significantly exhibit superior tumor‐killing ability under NIR laser irradiation in vivo. Collectively, these results demonstrate that nano‐TiO2‐coated MCNTs with NIR laser irradiation may serve as an effective strategy for the treatment of CRC.

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Cyclin A1, the alternative A-type cyclin, contributes to G1/S cell cycle progression in somatic cells

Cited by 89 publications

References 22 publications

DNA damage response involves modulation of Ku70 and Rb functions by cyclin A1 in leukemia cells

DNA damage response involves modulation of Ku70 and Rb functions by cyclin A1 in leukemia cells

Inhibitor of Cyclin-dependent Kinase (CDK) Interacting with Cyclin A1 (INCA1) Regulates Proliferation and Is Repressed by Oncogenic Signaling

Nano‐Titanium Oxide‐Coated Carbon Nanotubes for Photothermal Therapy in the Treatment of Colorectal Cancer

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