Id1 Gene Transfer Confers Angiogenic Property on Fully Differentiated Endothelial Cells and Contributes to Therapeutic Angiogenesis

Nishiyama, Koichi; Takaji, Kentaro; Kataoka, Kazunori; Kurihara, Yukiko; Yoshimura, Michihiro; Kato, Atsushi; Ogawa, Hisao; Kurihara, Hiroki

doi:10.1161/circulationaha.104.516898

Cited by 59 publications

(53 citation statements)

References 49 publications

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“…Plasmids and Construction of Id1 Mutants-The mouse Id1 cDNA was cloned as described previously (5). For construction of the N-or C-terminally GFP-tagged Id1, an Id1 cDNA fragment was inserted into the XhoI/EcoRI sites of the pEGFP-C2 expression vector (Clontech) or the XhoI/BamHI sites of the pEGFP-N3 expression vector (Clontech).…”

Section: Methodsmentioning

confidence: 99%

“…Id lacks a basic DNA binding domain and acts primarily as a transcriptional inhibitor of basic HLH transcriptional factors by inhibiting DNA binding and subsequent activation of transcription via heterodimerization (3). Recent evidence (5)(6)(7)(8)(9)(10)(11) suggests that Id1 and Id3 play pivotal roles in regulating developmental and postnatal angiogenesis. Complete loss of Id1 and Id3 genes resulted in vascular malformation in the forebrain and thereby in brain hemorrhage (10).…”

Section: Id1mentioning

confidence: 99%

“…With partial loss of these genes, neo-angiogenesis is blocked in tumor xenografts and spontaneous tumors (6 -8, 11). Ectopic expression of Id1 in ECs enhanced angiogenicity in both in vitro and in vivo angiogenesis models (5,9). To date, ␣6 and ␤4 integrins (7), matrix metalloprotease-2 (7), fibroblast growth factor receptor 1 (7), chemokine receptor 4 (11), and angiopoietin-1 (5) have been suggested to be downstream molecules of Id proteins.…”

Section: Id1mentioning

confidence: 99%

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Protein Kinase A-regulated Nucleocytoplasmic Shuttling of Id1 during Angiogenesis

Nishiyama

Takaji

Uchijima

et al. 2007

Journal of Biological Chemistry

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Id1, an inhibitory partner of basic-helix-loop-helix transcriptional factors, has recently been recognized as a potent contributor to angiogenesis. However, the molecular mechanism underlying its role in angiogenesis remains essentially unknown. Herein we demonstrate the subcellular localization of Id1 to be altered depending on the cellular context of vascular endothelial cells. Id1 was localized in the nuclei of human umbilical vein endothelial cells (HUVECs) cultured on uncoated plates, whereas it was translocated to the cytoplasm in HUVECs on Matrigel along with the formation of capillary-like structures. Treatment with the nuclear export inhibitor leptomycin B and mutagenesis analysis using green fluorescent protein-fused Id1 revealed CRM1/exportin-dependent nuclear export of Id1 in HUVECs on Matrigel. This nuclear export of Id1 was inhibited by protein kinase A (PKA) activation by dibutyryl cyclic AMP and forskolin but was promoted by PKA inactivation by H-89 and MDL-12,330A. Mutagenesis analysis of Id1 showed the phosphorylation of Ser-5 to possibly mediate the effect of PKA. These results suggest the function of Id1 as a transcriptional factor to be controlled by nucleocytoplasmic shuttling during angiogenesis and that PKA might be involved in this process. This may serve as a novel mechanism regulating angiogenesis and as a possible target for therapeutic vascular regeneration.

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Section: Methodsmentioning

confidence: 99%

Section: Id1mentioning

confidence: 99%

Section: Id1mentioning

confidence: 99%

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Protein Kinase A-regulated Nucleocytoplasmic Shuttling of Id1 during Angiogenesis

Nishiyama

Takaji

Uchijima

et al. 2007

Journal of Biological Chemistry

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“…Increased expression of ID1 has been shown to be associated with decreased cell differentiation and enhanced cell proliferation (39,40). ID1 has been shown to induce proliferation by transcriptionally inhibiting the expression of cyclin-dependent kinase (CDK) inhibitors p16, p21, p27, and p57 (41).…”

mentioning

confidence: 99%

ID1 Facilitates the Growth and Metastasis of Non-Small Cell Lung Cancer in Response to Nicotinic Acetylcholine Receptor and Epidermal Growth Factor Receptor Signaling

Pillai

Rizwani

et al. 2011

Molecular and Cellular Biology

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“…Recent evidence suggests that Id1 and Id3 play pivotal roles in regulating developmental and postnatal angiogenesis [7]. Id proteins play a role in the regulating of cell growth and differentiation when over-expressed and have also been implicated to induce malignant transformation [6].…”

Section: Introductionmentioning

confidence: 99%

Over-expression of Id2 and Id3 Proteins Regulates Growth and Survival of Human Colon Carcinoma (HCT116) Cells

2017

J App Biol Biotech

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Inhibitor of differentiation (Id) proteins are members of the Helix-Loop-Helix (HLH) group of transcription factors. These proteins uniquely have no DNA-binding domain and they play vital roles in cell growth, differentiation, senescence, apoptosis, angiogenesis and neoplastic transformation. Objective: This work investigated the pro-apoptotic functions of Id proteins and their loss-or gain-of function mutants to delimit the functional domains that are essential for apoptosis in an in vitro model using human epithelial colon carcinoma cell line (HCT116). Plasmids encoding Id1, Id2, Id3 and Id4 proteins were transiently over-expressed in cultured HCT116. Initially, cell proliferation assay with MTT (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) was performed, followed by apoptotic and cell cycle analyses on the transfected cells. Apoptotic and cell cycle profiles were generated and statistically analyzed. Id3 protein exhibited a pro-apoptotic effect in colorectal cancer cell lines (HCT116). In addition, over-expression of Id3 resulted in growth arrest in HCT116. Id2 Asp5 showed a pro-apoptotic whilst Id2 Ala5 and Id2 HB enhanced viability of HCT116. These findings suggest that Id2 Asp5 may be loss-of-function mutant in HCT116 lines. The aspartate mutant of Id3 (Id3 Asp5) was observed to be pro-apoptotic. However Id3 Ala5 and Id3 HB showed an anti-apoptotic effect. These findings suggest that Id2 Asp5, Id3 Ala5, Id3 HB and Id3NLS may be loss-of-function mutants in HCT116 whilst Id2 Ala5, Id2 HB and Id3 Asp5 are gain-of-function mutants. These results may suggest that Id2 and Id3 may play essential roles in modulating human epithelial colon carcinoma growth and survival and could provide some hope for therapeutic opportunities in the treatment of colonic cancers.

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Id1 Gene Transfer Confers Angiogenic Property on Fully Differentiated Endothelial Cells and Contributes to Therapeutic Angiogenesis

Cited by 59 publications

References 49 publications

Protein Kinase A-regulated Nucleocytoplasmic Shuttling of Id1 during Angiogenesis

Protein Kinase A-regulated Nucleocytoplasmic Shuttling of Id1 during Angiogenesis

ID1 Facilitates the Growth and Metastasis of Non-Small Cell Lung Cancer in Response to Nicotinic Acetylcholine Receptor and Epidermal Growth Factor Receptor Signaling

Over-expression of Id2 and Id3 Proteins Regulates Growth and Survival of Human Colon Carcinoma (HCT116) Cells

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