Interferon-γ Modulates a p53-independent Apoptotic Pathway and Apoptosis-related Gene Expression

Ossina, Natalya; Cannas, Angela; Powers, V C; Fitzpatrick, Paul; Knight, Joy; Gilbert, Jayne; Shekhtman, Eugene; Tomei, Licia; Umansky, Samuil R.; Kiefer, Michael

doi:10.1074/jbc.272.26.16351

Cited by 261 publications

(212 citation statements)

References 47 publications

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“…It is possible that this difference is cell line specific, or is influenced by the expression of recombinant proteins. For instance, the CHO IFN-c cell line in the study by Wong et al produces a recombinant human interferon gamma, which has been documented to activate Fas death receptor signaling (Curtin and Cotter 2003;Ossina et al 1997;Spanaus et al 1998). Therefore, the observed transcriptional changes in the CHO IFNc batch culture might not be universally applicable to other CHO cell lines.…”

Section: Discussionmentioning

confidence: 99%

Proteomics analysis of chinese hamster ovary cells undergoing apoptosis during prolonged cultivation

et al. 2011

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The degradation of environmental conditions, such as nutrient depletion and accumulation of toxic waste products over time, often lead to premature apoptotic cell death in mammalian cell cultures and suboptimal protein yield. Although apoptosis has been extensively researched, the changes in the whole cell proteome during prolonged cultivation, where apoptosis is a major mode of cell death, have not been examined. To our knowledge, the work presented here is the first whole cell proteome analysis of non-induced apoptosis in mammalian cells. Flow cytometry analyses of various activated caspases demonstrated the onset of apoptosis in Chinese hamster ovary cells during prolonged cultivation was primarily through the intrinsic pathway. Differential in gel electrophoresis proteomic study comparing protein samples collected during cultivation resulted in the identification of 40 differentially expressed proteins, including four cytoskeletal proteins, ten chaperone and folding proteins, seven metabolic enzymes and seven other proteins of varied functions. The induction of seven ER chaperones and foldases is a solid indication of the onset of the unfolded protein response, which is triggered by cellular and ER stresses, many of which occur during prolonged batch cultures. In addition, the upregulation of six glycolytic enzymes and another metabolic protein emphasizes that a change in the energy metabolism likely occurred as culture conditions degraded and apoptosis advanced. By identifying the intracellular changes during cultivation, this study provides a foundation for optimizing cell line-specific cultivation processes, prolonging longevity and maximizing protein production.

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Section: Discussionmentioning

confidence: 99%

Proteomics analysis of chinese hamster ovary cells undergoing apoptosis during prolonged cultivation

et al. 2011

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“…It has been proposed that IRF-1 interacts with Signal Transducers and Activator of Transcription (STATs) to induce the expression of caspase genes (Kumar et al, 1997;Hoey, 1997). IRF-1 has been implicated also in apoptosis induced by IFNg in human colon adenocarcinoma HT-29 cells treated with various cytotoxic agents (Ossina et al, 1997), in apoptosis of serum deprived and angiotensin II treated R3T3 cells (Horiuchi et al, 1997), and apoptosis of PKR de®cient MEFs that were resistant to death induced by double-stranded RNA, TNFa, or LPS .…”

Section: Terminal DI Erentiation Negative Growth Control and Myd Genesmentioning

confidence: 99%

MyD genes in negative growth control

Liebermann

Hoffman

1998

Oncogene

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“…IRF-1 plays an important role in p53-independent response to DNA damage and is able to promote apoptosis in p53(À) cells (Tamura et al, 1995;Ossina et al, 1997;Porta et al, 2005). There is evidence that IRF-1 may act in parallel with p53 to promote apoptosis and therefore, loss of IRF-1 would promote the survival of HMECs that had acutely lost p53 function.…”

Section: Discussionmentioning

confidence: 99%

“…rECM promotes recruitment of CBP and STAT1 to the IRF-1 GAS element Type II-IFN (IFN-g) signaling has been shown to promote p53-independent apoptosis (Ossina et al, 1997;Porta et al, 2005). We previously demonstrated that treatment of *HMEC-E6 cells with 1.0 mM Tam promotes formation of a STAT1 complex on the IRF-1 GAS element, recruitment of cofactor CBP and upregulation of IRF-1 messenger RNA (mRNA).…”

Section: Recm-induced Gene Transcriptsmentioning

confidence: 99%

Interferon regulatory factor-1 regulates reconstituted extracellular matrix (rECM)-mediated apoptosis in human mammary epithelial cells

et al. 2006

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Interactions between extracellular matrix (ECM) and mammary epithelial cells are critical for mammary gland homeostasis and apoptotic signaling. Interferon regulatory factor-1 (IRF-1) is a transcriptional regulator that promotes apoptosis during mammary gland involution and p53-independent apoptosis. We have recently shown that rapid cell surface tamoxifen (Tam) signaling promotes apoptosis in normal human mammary epithelial cells that were acutely damaged by expression of human papillomavirus type-16 E6 protein (*HMEC-E6). Apoptosis was mediated by recruitment of CREB-binding protein (CBP) to the c-activating sequence (GAS) element of the IRF-1 promoter, induction of IRF-1 and caspase-1/-3 activation. Here, we show that growth factor-depleted, reconstituted ECM (rECM), similar to Tam, promotes apoptosis in *HMEC-E6 cells through induction of IRF-1. Apoptosis was temporally associated with recruitment of CBP to the GAS element of the IRF-1 promoter, induction of IRF-1 expression and caspase-1/-3 activation. Small interfering RNA-mediated suppression of IRF-1 protein expression in *HMEC-E6 cells blocked (1) induction of IRF-1, (2) caspase-1/-3 activation and (3) apoptosis. These observations demonstrate that IRF-1 promotes rECM-mediated apoptosis and provide evidence that both rECM and rapid Tam signaling transcriptionally activate IRF-1 through recruitment of CBP to the IRF-1 GAS promoter complex.

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Interferon-γ Modulates a p53-independent Apoptotic Pathway and Apoptosis-related Gene Expression

Cited by 261 publications

References 47 publications

Proteomics analysis of chinese hamster ovary cells undergoing apoptosis during prolonged cultivation

Proteomics analysis of chinese hamster ovary cells undergoing apoptosis during prolonged cultivation

MyD genes in negative growth control

Interferon regulatory factor-1 regulates reconstituted extracellular matrix (rECM)-mediated apoptosis in human mammary epithelial cells

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