2007
DOI: 10.1161/01.res.0000254704.92532.b9
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Critical Role for FoxO3a-Dependent Regulation of p21 CIP1/WAF1 in Response to Statin Signaling in Cardiac Myocytes

Abstract: Abstract-Statins are widely used clinical drugs that exert beneficial growth-suppressive effects in patients with cardiac hypertrophy. We investigated the role of the cell cycle inhibitor p21 CIP1/WAF1 (p21) in statin-dependent inhibition of hypertrophic growth in postmitotic cardiomyocytes. We demonstrate that lovastatin fails to inhibit cardiac hypertrophy to angiotensin II in p21 Ϫ/Ϫ mice and that reconstitution of p21 function by TAT.p21 protein transduction can rescue statin action in these otherwise norm… Show more

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Cited by 67 publications
(55 citation statements)
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References 48 publications
(33 reference statements)
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“…It functions as a tumor suppressor by regulating many genes that control diverse biological activities, including cell proliferation (Dijkers et al, 2000;Hauck et al, 2007) and apoptosis (Sunters et al, 2003;Li et al, 2007). In this study, we found that overexpression of FoxO3a induced, while silencing of FoxO3a decreased, CCNG2 promoter activity.…”
Section: Nodal Induces Cyclin G2 Transcription Via Foxo3a G Fu and C mentioning
confidence: 59%
“…It functions as a tumor suppressor by regulating many genes that control diverse biological activities, including cell proliferation (Dijkers et al, 2000;Hauck et al, 2007) and apoptosis (Sunters et al, 2003;Li et al, 2007). In this study, we found that overexpression of FoxO3a induced, while silencing of FoxO3a decreased, CCNG2 promoter activity.…”
Section: Nodal Induces Cyclin G2 Transcription Via Foxo3a G Fu and C mentioning
confidence: 59%
“…23) p21 has a wide specificity for substrates such as CDK4/6, CDK2, and Cdc2, leading to cell cycle arrest at multiple phases. 22 27,[32][33][34] Because ANP gene expression is mediated by the transcription factor GATA-4 and signaling pathways leading to cardiomyocyte hypertrophy activate GATA-4 under various hypertrophic conditions, 35,36) upregulation of ANP gene expression suggests activation of a signaling pathway leading to the development of hypertrophy. It is possible that H 2 O 2 activated the hypertrophic signaling pathway in H9c2 cells even in the presence of BAPTA-AM.…”
Section: Discussionmentioning
confidence: 99%
“…FoxO3a activation increases cell cycle inhibitor proteins p21 and p27, both of which subsequently suppress G1 to S cell cycle transition [51][52][53][54] . Although p27 is transcriptionally regulated by FoxO3a via the PI3K/Aktdependent axis, it has been shown that p27 is also regulated via the FoxO3a/NF-κB/c-Myc-dependent pathway.…”
Section: Foxo3a Functionmentioning
confidence: 99%