Expression of VACM-1/cul5 mutant in endothelial cells induces MAPK phosphorylation and maspin degradation and converts cells to the angiogenic phenotype

Buchwalter, Abby; Dort, C. Van; Schultz, Sarah K.; Smith, Rob; Le, Ivanova; Abbott, J.L.; Oosterhouse, E.; Johnson, Alyssa E.; Hansen-Smith, Fay M.; Burnatowska-Hledin, Maria

doi:10.1016/j.mvr.2007.08.004

Cited by 18 publications

(27 citation statements)

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“…In our search for the biological activity of VACM-1, we showed that the expression of VACM-1/cul5 cDNA in several cell lines decreases cellular proliferation by a mechanism that involves attenuated cAMP production, decreased phosphorylation of mitogen-activating protein kinase (MAPK) and decreased nuclear localization of egr-1 gene product (Van Dort et al 2003, Johnson et al, 2007, Buchwalter et al, 2008. Our work also suggests that regulation of cellular signaling by VACM-1/cul5 may be cell-type dependent.…”

mentioning

confidence: 70%

“…Our work also suggests that regulation of cellular signaling by VACM-1/cul5 may be cell-type dependent. In a rat endothelial cell line, VACM-1/cul5 regulates expression of maspin (Buchwalter et al, 2008), in a breast cancer-derived cell line, T47D (Keydar et al, 1979), expression of VACM-1 cDNA attenuates estrogen-dependent increase in cell growth and decreases estrogen receptor concentrations in the nucleus (Johnson et al, 2007), while in cos 1 cells VACM-1/cul5 increases concentrations of the p53 tumor suppressor (Van Dort et al, 2003). A report that VACM-1/cul5 inhibits Src activity and suppresses Src-dependent tumorigenesis in mice (Lashlo and Cooper, 2009) further supports the role of VACM-1/cul5 in the regulation of cell growth.…”

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confidence: 99%

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Resveratrol enhances anti-proliferative effect of VACM-1/cul5 in T47D cancer cells

et al. 2010

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Vasopressin-activated calcium-mobilizing (VACM-1) protein is a cul-5 gene product that forms complexes with a subclass of ubiquitin E3 ligases involved in proteasomal protein degradation. The expression of VACM-1 cDNA in the T47D breast cancer cell line inhibits growth and decreases phosphorylation of mitogen activated protein kinase. Factors that regulate expression or stability of VACM-1 protein have not been identified, however. In our search to identify drugs/substances that may control VACM-1 protein expression, we examined the effects of resveratrol (trans-3,5,4'-trihydroxystilbene), a natural component in the human diet which inhibits tumor initiation and promotion. CMV vector and VACM-1 cDNA stably transfected T47D breast cancer-derived cells were treated with resveratrol and cell growth and VACM-1 protein concentrations were measured. Since the cellular mechanism of resveratrol-dependent inhibition of cell growth also involves the regulation of estrogen receptors, the effect of 17-β-estradiol and resveratrol on ERα levels and on cell growth was examined in control and in VACM-1 cDNA transfected cells. Our results demonstrate that antiproliferative effect of resveratrol observed in the control T47D cancer cells was significantly enhanced in VACM-1 cDNA transfected T47D cells. Western blot results indicated that resveratrol increased VACM-1 protein concentration. Finally, treatment with resveratrol for 24 and 48 h attenuated 17-β-estradiol induced increase in cell growth both in control and in VACM-1 cDNA transfected cells. The effect was significantly higher in the VACM-1 cDNA transfected cells when compared to controls. These results indicate that the antiproliferative effect of resveratrol may involve induction of VACM-1/cul5.

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confidence: 70%

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confidence: 99%

Resveratrol enhances anti-proliferative effect of VACM-1/cul5 in T47D cancer cells

et al. 2010

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“…2C). Interestingly, transfection of MDCK cells with a mutated VACM-1 cDNA ( S730A VACM-1 cDNA) previously shown to reverse cos 1 and rat endothelial cell phenotype [15,16] did not affect AQP2 levels in either control or Forskolin treated groups.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 95%

“…In both cell lines, the expression of VACM-1/cul5 may also compromise the forskolin-dependent translocation of AQP2 to the memrane. Interestingly, the expression of S730A VACM-1 cDNA, which reverses the inhibitory effect of VACM-1 on MAPK phosphorylation and cell growth [15] and compromises actin polymerization in rat endothelial cell line in vitro [16], did not affect AQP2 concentration in either the MDCK or cos 1 cells transfected with AQP2.…”

Section: Discusionmentioning

confidence: 96%

“…A 1:200 dilution of AQP2 antibody was used as recommended by the manufacturer. Affinity purified polyclonal antibodies directed against the amino (Ab-A) and the carboxy (Ab-B) termini of the rabbit VACM-1 protein characterized previously [14][15][16] were used at 1:200 dilution. To ascertain antibodies specificity against rat tissue, rat VACM-1 cDNA sequence was first determined by RT-PCR.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

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Aquaporin-2 Levelsin vitroandin vivoare Regulated by VACM-1, a Cul 5 Gene

Schultz

Andresen

et al. 2012

Cell Physiol Biochem

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Background: In the renal collecting duct, vasopressin regulates water permeability by a process that involves stimulation of adenylyl cyclase activity, cAMP production and subsequent translocation of water channel aquaporin-2 (AQP2) into the apical plasma membrane. We have previously shown that in cos 1 cells in vitro, both adenylyl cyclase activity and cAMP production can be regulated by VACM-1, a cul 5 gene that forms complexes involved in protein ubiquitination and subsequent degradation. Methods: To extend these observations further, the effects of changes in hydration state on the expression of VACM-1 at the mRNA and the protein level were examined in rats deprived of water (WD) for 24 hrs. Results: In the kidney of WD rats Western blot analyses of kidney tissue showed that the decrease in VACM-1 protein concentration was correlated with the increase in the AQP2 protein level. The immunostaining data suggested that VACM-1/cul5 may be decreased in renal collecting duct but increases in the vasculature of the inner medullary region in response to WD. To determine the possible consequences of the WD dependent decrease in VACM-1/cul5, we next examined the effects of VACM-1 expression on AQP2 protein in vitro. Immunocytochemistry and Western blot analyses data indicate that VACM-1/cul5 expression in MDCK line stably expressing AQP2 gene and in cos 1 cells co-transfected with the AQP2 and VACM-1/cul5 cDNAs decreased AQP2 protein concentration when compared to the vector transfected control groups. Conclusion: In summary, our data demonstrate that VACM-1 is involved in the regulation of AQP2 protein concentration and may play a role in regulating water balance.

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VACM-1/cul5 expression in vascular tissue in vivo is induced by water deprivation and its expression in vitro regulates aquaporin-1 concentrations

Johnson

Andresen

et al. 2012

Cell Tissue Res

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VACM-1, a cul5 gene product, when overexpressed in vitro, has an antiproliferative effect. In vivo, VACM-1/cul5 is present in tissues involved in the regulation of water balance. Neither proteins targeted for VACM-1/cul5-specific degradation nor factors that may regulate its expression in those tissues have been studied. To identify genes that may be misregulated by VACM-1 cDNA, we performed microarray analysis. Our results indicate that in cos-1 cells transfected with VACM-1 cDNA, mRNA levels for several genes, including AQP1, were decreased when compared to the control group. Our results also indicate that in cos-1 cells transfected with VACM-1 cDNA, endogenous AQP1 protein was decreased about 6-fold when compared to the controls. To test the hypothesis that VACM-1/cul5 may be regulated by conditions that compromise water homeostasis in vivo, we determined if 24 h of water deprivation affects VACM-1/cul5 levels or the effect of VACM-1/cul5 on AQP1. VACM-1 mRNA and protein levels were significantly higher in rat mesenteric arteries, skeletal muscle and the heart ventricle but not in the heart atrium from 24-h water-deprived rats when compared to the controls. Interestingly, 24 h of water deprivation increased modification of VACM-1 by an ubiquitin-like protein, Nedd8, essential for cullin-dependent E3 ligase activity. Although water deprivation did not significantly change AQP1 levels in the mesenteric arteries, AQP1 protein concentrations were inversely correlated with the ratio of the VACM-1 to Nedd8-modified VACM-1. These results suggest that VACM-1/cul5 may regulate endothelial AQP1 concentration both in vivo and in vitro.

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Expression of VACM-1/cul5 mutant in endothelial cells induces MAPK phosphorylation and maspin degradation and converts cells to the angiogenic phenotype

Cited by 18 publications

References 50 publications

Resveratrol enhances anti-proliferative effect of VACM-1/cul5 in T47D cancer cells

Resveratrol enhances anti-proliferative effect of VACM-1/cul5 in T47D cancer cells

Aquaporin-2 Levelsin vitroandin vivoare Regulated by VACM-1, a Cul 5 Gene

VACM-1/cul5 expression in vascular tissue in vivo is induced by water deprivation and its expression in vitro regulates aquaporin-1 concentrations

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