Cyclin-A1 | ScienceGate

ABSTRACT Gene expression in mammalian organisms is regulated at multiple levels, including DNA accessibility for transcription factors and chromatin structure. Methylation of CpG dinucleotides is thought to be involved in imprinting and in the pathogenesis of cancer. However, the relevance of methylation for directing tissue-specific gene expression is highly controversial. The cyclin A1 gene is expressed in very few tissues, with high levels restricted to spermatogenesis and leukemic blasts. Here, we show that methylation of the CpG island of the human cyclin A1 promoter was correlated with nonexpression in cell lines, and the methyl-CpG binding protein MeCP2 suppressed transcription from the methylated cyclin A1 promoter. Repression could be relieved by trichostatin A. Silencing of a cyclin A1 promoter-enhanced green fluorescent protein (EGFP) transgene in stable transfected MG63 osteosarcoma cells was also closely associated with de novo promoter methylation. Cyclin A1 could be strongly induced in nonexpressing cell lines by trichostatin A but not by 5-aza-cytidine. The cyclin A1 promoter-EGFP construct directed tissue-specific expression in male germ cells of transgenic mice. Expression in the testes of these mice was independent of promoter methylation, and even strong promoter methylation did not suppress promoter activity. MeCP2 expression was notably absent in EGFP-expressing cells. Transcription from the transgenic cyclin A1 promoter was repressed in most organs outside the testis, even when the promoter was not methylated. These data show the association of methylation with silencing of the cyclin A1 gene in cancer cell lines. However, appropriate tissue-specific repression of the cyclin A1 promoter occurs independently of CpG methylation.

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Functions of Cyclin A1 in the Cell Cycle and Its Interactions with Transcription Factor E2F-1 and the Rb Family of Proteins

Molecular and Cellular Biology ◽

10.1128/mcb.19.3.2400 ◽

1999 ◽

Vol 19 (3) ◽

pp. 2400-2407 ◽

Cited By ~ 94

Author(s):

Rong Yang ◽

Carsten Müller ◽

Vong Huynh ◽

Yuen K. Fung ◽

Amy S. Yee ◽

...

Keyword(s):

Cell Cycle ◽

Transcription Factor ◽

Mitotic Cell ◽

Histone H1 ◽

Mitotic Cell Cycle ◽

Osteosarcoma Cell ◽

Cell Cycle Regulators ◽

Cyclin A1 ◽

Transcription Factor E2f

ABSTRACT Human cyclin A1, a newly discovered cyclin, is expressed in testis and is thought to function in the meiotic cell cycle. Here, we show that the expression of human cyclin A1 and cyclin A1-associated kinase activities was regulated during the mitotic cell cycle. In the osteosarcoma cell line MG63, cyclin A1 mRNA and protein were present at very low levels in cells at the G0 phase. They increased during the progression of the cell cycle and reached the highest levels in the S and G2/M phases. Furthermore, the cyclin A1-associated histone H1 kinase activity peaked at the G2/M phase. We report that cyclin A1 could bind to important cell cycle regulators: the Rb family of proteins, the transcription factor E2F-1, and the p21 family of proteins. The in vitro interaction of cyclin A1 with E2F-1 was greatly enhanced when cyclin A1 was complexed with CDK2. Associations of cyclin A1 with Rb and E2F-1 were observed in vivo in several cell lines. When cyclin A1 was coexpressed with CDK2 in sf9 insect cells, the CDK2-cyclin A1 complex had kinase activities for histone H1, E2F-1, and the Rb family of proteins. Our results suggest that the Rb family of proteins and E2F-1 may be important targets for phosphorylation by the cyclin A1-associated kinase. Cyclin A1 may function in the mitotic cell cycle in certain cells.

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Cyclin A1: CCNA1

Encyclopedia of Signaling Molecules ◽

10.1007/978-3-319-67199-4_100903 ◽

2018 ◽

pp. 1259-1259

Keyword(s):

Cyclin A1

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Cyclin A1-deficient mice lack histone H3 serine 10 phosphorylation and exhibit altered aurora B dynamics in late prophase of male meiosis

Developmental Biology ◽

10.1016/j.ydbio.2007.04.009 ◽

2007 ◽

Vol 306 (2) ◽

pp. 725-735 ◽

Cited By ~ 32

Author(s):

Helen D. Nickerson ◽

Ayesha Joshi ◽

Debra J. Wolgemuth

Keyword(s):

Histone H3 ◽

Male Meiosis ◽

Aurora B ◽

Cyclin A1 ◽

Late Prophase ◽

Deficient Mice

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Promoter methylation of P16, RARβ, E-cadherin, cyclin A1 and cytoglobin in oral cancer: quantitative evaluation using pyrosequencing

British Journal of Cancer ◽

10.1038/sj.bjc.6602972 ◽

2006 ◽

Vol 94 (4) ◽

pp. 561-568 ◽

Cited By ~ 143

Author(s):

R J Shaw ◽

T Liloglou ◽

S N Rogers ◽

J S Brown ◽

E D Vaughan ◽

...

Keyword(s):

Oral Cancer ◽

Quantitative Evaluation ◽

Promoter Methylation ◽

Cyclin A1 ◽

E Cadherin

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A distinct cyclin A is expressed in germ cells in the mouse

Development ◽

10.1242/dev.122.1.53 ◽

1996 ◽

Vol 122 (1) ◽

pp. 53-64 ◽

Cited By ~ 5

Author(s):

C. Sweeney ◽

M. Murphy ◽

M. Kubelka ◽

S.E. Ravnik ◽

C.F. Hawkins ◽

...

Keyword(s):

Cell Cycle ◽

Germ Cells ◽

Cyclin A ◽

Cyclin A1 ◽

Late Pachytene ◽

Sequence Identity ◽

Somatic Tissues ◽

Cyclin A2 ◽

Pachytene Spermatocytes ◽

Metaphase Ii Oocytes

In this paper, the existence of two A-type cyclins in the mouse is demonstrated. In the adult mouse, the expression of cyclin A1, which has greatest sequence identity with Xenopus cyclin A1, is restricted to germ cells. In contrast cyclin A2, which has greatest sequence identity with human cyclin A and Xenopus cyclin A2, is expressed in all tissues analysed. In order to explore the function of cyclin A1 in germ cells, its expression during the meiotic cell cycle and its associated kinase subunits have been characterised in the testis. The levels of cyclin A1 mRNA rise dramatically in late pachytene spermatocytes and become undetectable soon after completion of the meiotic divisions; thus its expression is cell cycle regulated. In lysates of germ cells from adult testes, cyclin A1 is present in p13suc1 precipitates, and cyclin A1 immunoprecipitates possess histone H1 kinase activity. Three kinase partners of cyclin A1 were identified: p34cdc2, a polypeptide of 39 × 10(3) M(r) that is related to p33cdk2 and, in lesser quantities, p33cdk2. Cyclin A1 was also detected in oocytes; in metaphase I and metaphase II oocytes, a proportion of the cyclin A1 colocalises with the spindle, possibly suggestive of a functional interaction. These data indicate that mammalian germ cells contain cyclin A1-dependent kinases that either act as a substitute for, or in addition to, the cyclin A2-dependent kinases characterised in somatic tissues.

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MicroRNA-372 Is Down-regulated and Targets Cyclin-dependent Kinase 2 (CDK2) and Cyclin A1 in Human Cervical Cancer, Which May Contribute to Tumorigenesis

Journal of Biological Chemistry ◽

10.1074/jbc.m111.221564 ◽

2011 ◽

Vol 286 (29) ◽

pp. 25556-25563 ◽

Cited By ~ 65

Author(s):

Rui-Qing Tian ◽

Xing-Hua Wang ◽

Li-Juan Hou ◽

Wei-Hua Jia ◽

Qian Yang ◽

...

Keyword(s):

Cervical Cancer ◽

Cyclin Dependent Kinase ◽

Cyclin A1 ◽

Human Cervical Cancer

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Hexokinase 2 Promotes Cell Growth and Tumor Formation Through the Raf/MEK/ERK Signaling Pathway in Cervical Cancer

Frontiers in Oncology ◽

10.3389/fonc.2020.581208 ◽

2020 ◽

Vol 10 ◽

Author(s):

Nan Cui ◽

Lu Li ◽

Qian Feng ◽

Hong-mei Ma ◽

Dan Lei ◽

...

Keyword(s):

Cervical Cancer ◽

Cell Growth ◽

Cancer Cells ◽

Signaling Pathway ◽

Hela Cells ◽

Tumor Formation ◽

Erk Signaling ◽

Cyclin A1 ◽

Hexokinase 2 ◽

Cervical Cancer Cells

Hexokinase 2 (HK2) is a member of the hexokinases (HK) that has been reported to be a key regulator during glucose metabolism linked to malignant growth in many types of cancers. In this study, stimulation of HK2 expression was observed in squamous cervical cancer (SCC) tissues, and HK2 expression promoted the proliferation of cervical cancer cells in vitro and tumor formation in vivo by accelerating cell cycle progression, upregulating cyclin A1, and downregulating p27 expression. Moreover, transcriptome sequencing analysis revealed that MAPK3 (ERK1) was upregulated in HK2-overexpressing HeLa cells. Further experiments found that the protein levels of p-Raf, p-MEK1/2, ERK1/2, and p-ERK1/2 were increased in HK2 over-expressing SiHa and HeLa cells. When ERK1/2 and p-ERK1/2 expression was blocked by an inhibitor (FR180204), reduced cyclin A1 expression was observed in HK2 over-expressing cells, with induced p27 expression and inhibited cell growth. Therefore, our data demonstrated that HK2 promoted the proliferation of cervical cancer cells by upregulating cyclin A1 and down-regulating p27 expression through the Raf/MEK/ERK signaling pathway.

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