Key Spec Table
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|M, R||IP, WB, ICC||M||Purified||Monoclonal Antibody|
|Presentation||0.1M Tris-glycine, pH 7.4, 0.15M NaCl, 0.05% sodium azide before the addition of glycerol to 30%|
|Safety Information according to GHS|
|Storage and Shipping Information|
|Storage Conditions||Stable for 2 years at -20°C|
|Material Size||100 µg|
|Anti-Cyclin D1 (mouse monoclonal IgG1) - 2410234||2410234|
|Anti-Cyclin D1 (mouse monoclonal IgG1)||2867978|
|Anti-Cyclin D1 - 26958||26958|
|Reference overview||Pub Med ID|
|Myocardin related transcription factors are required for coordinated cell cycle progression.|
Shaposhnikov, D; Kuffer, C; Storchova, Z; Posern, G
Cell cycle (Georgetown, Tex.) 12 1762-72 2013
Myocardin related transcription factors A and B (MRTFs) activate serum response factor-driven transcription in response to Rho signaling and changes in actin dynamics. Myocardin and MRTFs have been implicated in anti-proliferative effects on a range of cell types. The precise mechanisms, however, remained elusive. We employed double knockdown of MRTF-A and MRTF-B in NIH 3T3 fibroblasts to evaluate its effects on cell cycle progression and proliferation. We show that transient depletion of MRTFs conveys a modest anti-proliferative effect and impinges on normal cell cycle progression, resulting in significantly shortened G 1 phase and slightly extended S and G 2 phase under normal growth conditions. Under serum-starved conditions we observed aberrant entry into the S and G 2 phases without subsequent cell division. This was accompanied by downregulation of cyclin-CDK inhibitors p27Kip1, p18Ink4c and 19Ink4d as well as upregulation of p21Waf1 and cyclin D1. Extended knockdown led to increased formation of micronuclei, while cells stably depleted of MRTFs tend to become aneuploid and polyploid. Thus, MRTFs are required for accurate cell cycle progression and maintenance of genomic stability in fibroblast cells.
|Overexpression of HOXB5, cyclin D1 and PCNA in congenital cystic adenomatoid malformation.|
Xiangyuan Wang,Debra J Wolgemuth,Laxmi V Baxi
Fetal diagnosis and therapy 29 2011
We investigated the patterns of expression of HOXB5, cyclin D1 and proliferating cell nuclear antigen (PCNA) proteins in human congenital cystic adenomatoid malformation (CCAM) to establish the molecular basis of its etiology.
|Deficiency of the NR4A neuron-derived orphan receptor-1 attenuates neointima formation after vascular injury.|
Nomiyama, T; Zhao, Y; Gizard, F; Findeisen, HM; Heywood, EB; Jones, KL; Conneely, OM; Bruemmer, D
Circulation 119 577-86 2009
The neuron-derived orphan receptor-1 (NOR1) belongs to the evolutionary highly conserved and most ancient NR4A subfamily of the nuclear hormone receptor superfamily. Members of this subfamily function as early-response genes regulating key cellular processes, including proliferation, differentiation, and survival. Although NOR1 has previously been demonstrated to be required for smooth muscle cell proliferation in vitro, the role of this nuclear receptor for the proliferative response underlying neointima formation and target genes trans-activated by NOR1 remain to be defined.Using a model of guidewire-induced arterial injury, we demonstrate decreased neointima formation in NOR1(-/-) mice compared with wild-type mice. In vitro, NOR1-deficient smooth muscle cells exhibit decreased proliferation as a result of a G(1)--greater than S phase arrest of the cell cycle and increased apoptosis in response to serum deprivation. NOR1 deficiency alters phosphorylation of the retinoblastoma protein by preventing mitogen-induced cyclin D1 and D2 expression. Conversely, overexpression of NOR1 induces cyclin D1 expression and the transcriptional activity of the cyclin D1 promoter in transient reporter assays. Gel shift and chromatin immunoprecipitation assays identified a putative response element for NR4A receptors in the cyclin D1 promoter, to which NOR1 is recruited in response to mitogenic stimulation. Finally, we provide evidence that these observations are applicable in vivo by demonstrating decreased cyclin D1 expression during neointima formation in NOR1-deficient mice.These experiments characterize cyclin D1 as an NOR1-regulated target gene in smooth muscle cells and demonstrate that NOR1 deficiency decreases neointima formation in response to vascular injury.
|Nerve Growth factor regulation of cyclin D1 in PC12 cells through a p21RAS extracellular signal-regulated kinase pathway requires cooperative interactions between Sp1 and nuclear factor-kappaB.|
Marampon, F; Casimiro, MC; Fu, M; Powell, MJ; Popov, VM; Lindsay, J; Zani, BM; Ciccarelli, C; Watanabe, G; Lee, RJ; Pestell, RG
Molecular biology of the cell 19 2566-78 2008
The PC12 pheochromocytoma cell line responds to nerve growth factor (NGF) by exiting from the cell cycle and differentiating to induce extending neurites. Cyclin D1 is an important regulator of G1/S phase cell cycle progression, and it is known to play a role in myocyte differentiation in cultured cells. Herein, NGF induced cyclin D1 promoter, mRNA, and protein expression via the p21(RAS) pathway. Antisense- or small interfering RNA to cyclin D1 abolished NGF-mediated neurite outgrowth, demonstrating the essential role of cyclin D1 in NGF-mediated differentiation. Expression vectors encoding mutants of the Ras/mitogen-activated protein kinase pathway, and chemical inhibitors, demonstrated NGF induction of cyclin D1 involved cooperative interactions of extracellular signal-regulated kinase, p38, and phosphatidylinositol 3-kinase pathways downstream of p21(RAS). NGF induced the cyclin D1 promoter via Sp1, nuclear factor-kappaB, and cAMP-response element/activated transcription factor sites. NGF induction via Sp1 involved the formation of a Sp1/p50/p107 complex. Cyclin D1 induction by NGF governs differentiation and neurite outgrowth in PC12 cells.Full Text Article
|Regulation of PGC-1alpha and PGC-1alpha-responsive genes with forskolin-induced Schwann cell differentiation.|
Cowell, RM; Blake, KR; Inoue, T; Russell, JW
Neuroscience letters 439 269-74 2008
Recent evidence indicates that mitochondrial homeostasis is critical for myelination and maintenance of peripheral nerve function. Mice lacking the metabolic transcriptional coactivator peroxisome proliferator activated receptor gamma coactivator 1alpha (PGC-1alpha) show reductions in expression of myelin-related proteins and exhibit myelin-associated lesions, so we identified PGC-1alpha target genes in Schwann cells (SCs) in vitro to determine potential roles for PGC-1alpha in glia and tested whether PGC-1alpha was sufficient for SC differentiation and myelination. Forskolin-induced differentiation was associated with an upregulation of PGC-1alpha mRNA and protein, and while overexpression of PGC-1alpha upregulated genes such as manganese superoxide dismutase and estrogen-related receptor alpha, it was not sufficient for induction of differentiation. Both PGC-1alpha overexpression and forskolin exposure caused an increase in the mitochondrial fusion-related protein mitofusin 1. These studies suggest that PGC-1alpha might be a potential target to promote mitochondrial stability during differentiation and myelination.
|Human cytomegalovirus-encoded chemokine receptor US28 promotes tumorigenesis.|
Maussang, D; Verzijl, D; van Walsum, M; Leurs, R; Holl, J; Pleskoff, O; Michel, D; van Dongen, GA; Smit, MJ
Proceedings of the National Academy of Sciences of the United States of America 103 13068-73 2006
Human cytomegalovirus (HCMV) is a widely spread herpesvirus, suggested to play a role in tumor progression. US28, a chemokine receptor encoded by HCMV, binds a broad spectrum of chemokines and constitutively activates various pathways linked to proliferation. Our studies reveal that expression of US28 induces a proangiogenic and transformed phenotype by up-regulating the expression of vascular endothelial growth factor and enhancing cell growth and cell cycle progression. US28-expressing cells promote tumorigenesis when injected into nude mice. The G protein-uncoupled constitutively inactive mutant of US28, induces delayed and attenuated tumor formation, indicating the importance of constitutive receptor activity in the early onset of tumor development. Importantly, also in glioblastoma cells infected with the newly isolated clinical HCMV strain Titan, US28 was shown to be involved in the HCMV-induced angiogenic phenotype. Hence, the constitutively activated chemokine receptor US28 might act as a viral oncogene and enhance and/or promote HCMV-associated tumor progression.Full Text Article
|The NR4A orphan nuclear receptor NOR1 is induced by platelet-derived growth factor and mediates vascular smooth muscle cell proliferation.|
Nomiyama, T; Nakamachi, T; Gizard, F; Heywood, EB; Jones, KL; Ohkura, N; Kawamori, R; Conneely, OM; Bruemmer, D
The Journal of biological chemistry 281 33467-76 2006
Members of the nuclear hormone receptor superfamily function as key transcriptional regulators of inflammation and proliferation in cardiovascular diseases. In addition to the ligand-dependent peroxisome proliferator-activated receptors and liver X receptors, this family of transcription factors includes a large number of orphan receptors, and their role in vascular diseases remains to be investigated. The neuron-derived orphan receptor-1 (NOR1) belongs to the ligand-independent NR4A subfamily, which has been implicated in cell proliferation, differentiation, and apoptosis. In this study, we demonstrate NOR1 expression in vascular smooth muscle cells (SMC) of human atherosclerotic lesions. In response to mitogenic stimulation with platelet-derived growth factor (PDGF), SMC rapidly express NOR1 through an ERK-MAPK-dependent signaling pathway. 5'-deletion analysis, site-directed mutagenesis, and transactivation experiments demonstrate that PDGF-induced NOR1 expression is mediated through a cAMP-response element-binding protein (CREB)-dependent transactivation of the NOR1 promoter. Consequently, short interfering RNA-mediated depletion of CREB abolished PDGF-induced NOR1 expression in SMC. Furthermore, PDGF induced Ser-133 phosphorylation of CREB and subsequent binding to the CRE sites of the endogenous NOR1 promoter. Functional analysis demonstrated that PDGF induces NOR1 transactivation of its consensus NGFI-B-response elements (NBRE) in SMC. We finally demonstrate that SMC isolated from NOR1-deficient mice exhibit decreased cell proliferation and characterize cyclin D1 and D2 as NOR1 target genes in SMC. These experiments indicate that PDGF-induced NOR1 transcription in SMC is mediated through CREB-dependent transactivation of the NOR1 promoter and further demonstrate that NOR1 functions as a key transcriptional regulator of SMC proliferation.Full Text Article
|Identification of G1 kinase activity for cdk6, a novel cyclin D partner.|
Meyerson, M and Harlow, E
Mol. Cell. Biol., 14: 2077-86 (1994) 1994
A family of vertebrate cdc2-related kinases has been identified, and these kinases are candidates for roles in cell cycle regulation. Here, we show that the human PLSTIRE gene product is a novel cyclin-dependent kinase, cdk6. The cdk6 kinase is associated with cyclins D1, D2, and D3 in lysates of human cells and is activated by coexpression with D-type cyclins in Sf9 insect cells. Furthermore, we demonstrate that endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB, the product of the retinoblastoma tumor suppressor gene. The activation of cdk6 kinase occurs during mid-G1 in phytohemagglutinin-stimulated T cells, well prior to the activation of cdk2 kinase. This timing suggests that cdk6, and by analogy its homolog cdk4, links growth factor stimulation with the onset of cell cycle progression.
|Functional interactions of the retinoblastoma protein with mammalian D-type cyclins.|
Ewen, M E, et al.
Cell, 73: 487-97 (1993) 1993
The retinoblastoma gene product (Rb) can interact efficiently with two of three D-type G1 cyclins (D2 and D3) in vitro. Binding depended upon the minimal regions of Rb necessary for its growth-suppressive activity, as well as upon the D-type cyclin sequence motif shared with Rb-binding DNA tumor virus oncoproteins. Coexpression of the three D-type cyclins with the cyclin-dependent kinase (cdk4) in insect cells generated Rb kinase activity. By contrast, cyclins D2 and D3, but not D1, activated another such kinase, cdk2. Introduction of cyclin D2 and Rb into the Rb-deficient cell line SAOS-2 led to overt Rb hyperphosphorylation, whereas Rb, expressed alone or together with cyclin D1, remained unphosphorylated. Cyclin D2-dependent phosphorylation inhibited its binding to the transcription factor E2F and reversed the Rb G1 exit block in the cell cycle. Thus, all D-type cyclins do not function equivalently, and one of them plays a major role in reversing the cycle-blocking function of a known tumor suppressor.
|A possible new member of tyrosine kinase family, human frt sequence, is highly conserved in vertebrates and located on human chromosome 13.|
Matsushime, H, et al.
Jpn. J. Cancer Res., 78: 655-61 (1987) 1987
We have isolated a human genomic DNA (designated human frt) cross-hybridizing with the v-ros oncogene of UR2 sarcoma virus. Sequencing analysis of this fragment revealed that this sequence contains a 123-base-pair exon-like structure surrounded by consensus sequences of splice acceptor and donor sites. The deduced amino acid sequence of this stretch was highly homologous to a portion of a tyrosine kinase domain of src family. The human frt sequence was found to be conserved in a wide variety of vertebrates. By using a human-mouse hybridoma panel, human frt was located on chromosome 13, while human c-ros-1 was located on chromosome 6.