Caveolin-1 controls cell proliferation and cell death by suppressing expression of the inhibitor of apoptosis protein survivin

MIHA is an inhibitor of apoptosis protein (IAP) that can inhibit cell death by direct interaction with caspases, the effector proteases of apoptosis. DIABLO is a mammalian protein that can bind to IAPs and antagonize their antiapoptotic effect, a function analogous to that of the proapoptotic Drosophila molecules, Grim, Reaper, and HID. Here, we show that after UV radiation, MIHA prevented apoptosis by inhibiting caspase 9 and caspase 3 activation. Unlike Bcl-2, MIHA functioned after release of cytochrome c and DIABLO from the mitochondria and was able to bind to both processed caspase 9 and processed caspase 3 to prevent feedback activation of their zymogen forms. Once released into the cytosol, DIABLO bound to MIHA and disrupted its association with processed caspase 9, thereby allowing caspase 9 to activate caspase 3, resulting in apoptosis.

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Protein kinase C stabilizes X-linked inhibitor of apoptosis protein (XIAP) through phosphorylation at Ser87 to suppress apoptotic cell death

Psychogeriatrics ◽

10.1111/j.1479-8301.2011.00355.x ◽

2011 ◽

Vol 11 (2) ◽

pp. 90-97 ◽

Cited By ~ 12

Author(s):

Kiyoko KATO ◽

Toshihisa TANAKA ◽

Golam SADIK ◽

Miyako BABA ◽

Daisuke MARUYAMA ◽

...

Keyword(s):

Cell Death ◽

Protein Kinase C ◽

Protein Kinase ◽

Apoptotic Cell ◽

Apoptotic Cell Death ◽

Inhibitor Of Apoptosis ◽

Inhibitor Of Apoptosis Protein ◽

Kinase C ◽

Apoptosis Protein

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Amadori-glycated albumin-induced vascular smooth muscle cell proliferation and expression of inhibitor of apoptosis protein-1 and nerve growth factor-γ

BioFactors ◽

10.1002/biof.5520310301 ◽

2007 ◽

Vol 31 (3-4) ◽

pp. 145-153 ◽

Cited By ~ 8

Author(s):

Byung-Wan Lee ◽

Jahei Ihm ◽

Jun Gu Kang ◽

Moon Gi Choi ◽

Hyung Joon Yoo ◽

...

Keyword(s):

Cell Proliferation ◽

Smooth Muscle ◽

Nerve Growth Factor ◽

Growth Factor ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cell ◽

Glycated Albumin ◽

Inhibitor Of Apoptosis ◽

Inhibitor Of Apoptosis Protein ◽

Apoptosis Protein

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E-Cadherin Is Required for Caveolin-1-Mediated Down-Regulation of the Inhibitor of Apoptosis Protein Survivin via Reduced β-Catenin-Tcf/Lef-Dependent Transcription

Molecular and Cellular Biology ◽

10.1128/mcb.01991-06 ◽

2007 ◽

Vol 27 (21) ◽

pp. 7703-7717 ◽

Cited By ~ 75

Author(s):

Vicente A. Torres ◽

Julio C. Tapia ◽

Diego A. Rodriguez ◽

Alvaro Lladser ◽

Cristian Arredondo ◽

...

Keyword(s):

Tumor Suppressor ◽

Molecular Mechanisms ◽

Cell Model ◽

Survivin Expression ◽

Inhibitor Of Apoptosis ◽

Down Regulation ◽

Inhibitor Of Apoptosis Protein ◽

Caveolin 1 ◽

Apoptosis Protein ◽

E Cadherin

ABSTRACT Caveolin-1 reportedly acts as a tumor suppressor and promotes events associated with tumor progression, including metastasis. The molecular mechanisms underlying such radical differences in function are not understood. Recently, we showed that caveolin-1 inhibits expression of the inhibitor of apoptosis protein survivin via a transcriptional mechanism involving the β-catenin-Tcf/Lef pathway. Surprisingly, while caveolin-1 expression decreased survivin mRNA and protein levels in HT29(ATCC) human colon cancer cells, this was not the case in metastatic HT29(US) cells. Survivin down-regulation was paralleled by coimmunoprecipitation and colocalization of caveolin-1 with β-catenin in HT29(ATCC) but not HT29(US) cells. Unlike HT29(ATCC) cells, HT29(US) cells expressed small amounts of E-cadherin that accumulated in intracellular patches rather than at the cell surface. Re-expression of E-cadherin in HT29(US) cells restored the ability of caveolin-1 to down-regulate β-catenin-Tcf/Lef-dependent transcription and survivin expression, as seen in HT29(ATCC) cells. In addition, coimmunoprecipitation and colocalization between caveolin-1 and β-catenin increased upon E-cadherin expression in HT29(US) cells. In human embryonic kidney HEK293T and HT29(US) cells, caveolin-1 and E-cadherin cooperated in suppressing β-catenin-Tcf/Lef-dependent transcription as well as survivin expression. Finally, mouse melanoma B16-F10 cells, another metastatic cell model with low endogenous caveolin-1 and E-cadherin levels, were characterized. In these cells, caveolin-1-mediated down-regulation of survivin in the presence of E-cadherin coincided with increased apoptosis. Thus, the absence of E-cadherin severely compromises the ability of caveolin-1 to develop activities potentially relevant to its role as a tumor suppressor.

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MiR-489-3p modulates cell proliferation and apoptosis in cerulein-induced acute pancreatitis by targeting X-linked inhibitor of apoptosis protein

Archives of Medical Science ◽

10.5114/aoms/117736 ◽

2021 ◽

Author(s):

Xiang Li ◽

Hong Qin ◽

Xiaotong Han ◽

Xingwen Zhang ◽

Luping Wang ◽

...

Keyword(s):

Cell Proliferation ◽

Acute Pancreatitis ◽

Poor Prognosis ◽

Luciferase Assay ◽

Inhibitor Of Apoptosis ◽

Inhibitor Of Apoptosis Protein ◽

Immunoprecipitation Assay ◽

Apoptosis Protein ◽

Proliferation And Apoptosis ◽

Rna Immunoprecipitation

IntroductionThis study aims to explore the effect and mechanism of miR�489-3p on the proliferation and apoptosis of pancreatic acinar cells in acute pancreatitis (AP).Material and methodsX-linked inhibitor of apoptosis protein (XIAP) and miR-489-3p expression in serum of AP patients, pancreatic AR42J cells, and rat AP tissues were measured using quantitative reverse transcription poly�merase chain reaction and western blot. The effect of miR-489-3p on pro�liferation and apoptosis was determined by MTT assay and flow cytometry. The relationship between XIAP and miR-489-3p was verified using luciferase assay RNA immunoprecipitation assay. Histological changes in rat pancreatic tissues were observed via haematoxylin and eosin staining.ResultsMeasurement of miR-489-3p and XIAP expressions in AP patients revealed a negative correlation between miR-489-3p and XIAP. Increased miR-489-3p expression in AP patients indicated a poor prognosis. Cerulein was used to induce AP in AR42J cells and standard deviation rats. Exper�iments in cells and AP rat models showed that miR-489-3p can increase cell apoptosis and inhibit cell proliferation by regulating XIAP, as shown by elevated expressions of pro-apoptotic proteins (p53 and Bax) and decreased expression of proliferation indicator (Ki-67) after transfection of miR-489- 3p mimics. Meanwhile, knockdown of miR-489-3p abrogated the inhibitory effects of miR-489-3p on cell proliferation and the promotion on cell apop�tosis. Luciferase assay and RNA immunoprecipitation assay confirmed that XIAP can directly bind miR-489-3p.ConclusionsWe concluded that miR-489-3p modulates cell proliferation and apoptosis in AP by targeting XIAP. Given that high expression of miR�489-3p in AP indicated poor prognosis, it raises the possibility that miR�489-3p might be a novel and valuable therapeutic target and a prognosis indicator for AP.

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