E2F1 and c-Myc Potentiate Apoptosis through Inhibition of NF-κB Activity that Facilitates MnSOD-Mediated ROS Elimination

Tanaka, Hirokazu; Matsumura, Itaru; Ezoe, Sachiko; Satoh, Yusuke; Sakamaki, Toshiyuki; Albanese, Chris; Machii, Takashi; Pestell, Richard G.; Kanakura, Yuzuru

doi:10.1016/s1097-2765(02)00522-1

Cited by 281 publications

(239 citation statements)

References 37 publications

Supporting

Mentioning

207

Contrasting

Unclassified

Order By: Relevance

“…E2F competes with the p50 subunit of NF-kB resulting in NF-kB inactivation. Inactivation of NF-kB decreased MnSOD transcription, which could then result in increased ROS levels (Tanaka et al, 2002). These results further support the threshold concept of ROS function; lower levels of ROS are growth stimulatory, whereas higher levels of ROS are detrimental.…”

Section: Intracellular Redox State and Cell Cycle Proteinssupporting

confidence: 75%

“…As discussed earlier, entry into the S phase is preceded by a transient increase in prooxidant levels (Menon et al, 2003), which is consistent with a decrease in MnSOD activity in the S phase (Li and Oberley, 1998). However, persistent increase in E2F is deleterious and induces apoptosis in serumstarved NIH3T3 fibroblasts (Tanaka et al, 2002). E2F overexpression-induced apoptosis is associated with increased ROS levels and inactivation of MnSOD transcription.…”

Section: Intracellular Redox State and Cell Cycle Proteinssupporting

confidence: 57%

See 1 more Smart Citation

A redox cycle within the cell cycle: ring in the old with the new

2006

View full text Add to dashboard Cite

In recent years, the intracellular oxidation-reduction (redox) state has gained increasing attention as a critical mediator of cell signaling, gene expression changes and proliferation. This review discusses the evidence for a redox cycle (i.e., fluctuation in the cellular redox state) regulating the cell cycle. The presence of redox-sensitive motifs (cysteine residues, metal co-factors in kinases and phosphatases) in several cell cycle regulatory proteins indicate periodic oscillations in intracellular redox state could play a central role in regulating progression from G 0 /G 1 to S to G 2 and M cell cycle phases. Fluctuations in the intracellular redox state during cell cycle progression could represent a fundamental mechanism linking oxidative metabolic processes to cell cycle regulatory processes. Proliferative disorders are central to a variety of human pathophysiological conditions thought to involve oxidative stress. Therefore, a more complete understanding of redox control of the cell cycle could provide a biochemical rationale for manipulating aberrant cell proliferation.

show abstract

Section: Intracellular Redox State and Cell Cycle Proteinssupporting

confidence: 75%

Section: Intracellular Redox State and Cell Cycle Proteinssupporting

confidence: 57%

A redox cycle within the cell cycle: ring in the old with the new

2006

View full text Add to dashboard Cite

show abstract

“…Further, LMPIP may shorten G1/S transition through a decrease in pocket protein (RB) expression. Many studies also showed oxidative stress decreased RB phosphorylation, which blocked E2F1 release and the activation of G1/S regulators (Esposito et al, 2001;Tanaka et al, 2002). In this study, it was found that in LMPIP-transfected NPC cells, cyclin D and CDK were activated and higher levels of E2F1 expression were also detected, with concurrent decrease in RB expression.…”

Section: Discussionsupporting

confidence: 51%

Functional interaction of Ugene and EBV infection mediates tumorigenic effects

et al. 2011

View full text Add to dashboard Cite

Epstein-Barr virus (EBV) infection is associated with many human neoplasms, in which EBV-derived latent membrane protein-1 (LMP1) appears to be critical, but its exact oncogenic mechanism remains to be defined. To this end, our initial microarray analyses identified a LMP1-inducible gene, Ugene, originally characterized as a binding partner for uracil DNA glycosylase 2, which is highly expressed in malignant colon cancer. In this report, it was found that Ugene, designated herein as LMP1-induced protein (LMPIP), was induced, in a time-dependent manner, in EBV-infected peripheral blood mononuclear cells and LMP1-transfected 293 cells. Functionally, when compared with mock-transfected cells, overexpression of LMPIP in nasopharyngeal carcinoma (NPC) cell lines resulted in a decrease in reactive oxygen species production and maintained mitochondria membrane potential (Dw) loss induced by H 2 O 2 . The NPC cells transfected with LMPIP also showed a decrease in G1 population and an increase in the cell population in sub-G1 and multiploid phase, concomitant with increased levels of cell cycle activators, including cyclin D1 and CDK4. In contrast, silencing of LMPIP expression in the NPC tumor cell lines with short hairpin RNA interference revealed significantly decreased cell population at G1/S phase, while the number of cells in multiploid phase increased. Significantly, NPC cells with LMPIP knock-down also showed a decrease in tumorigenic and transforming activity induced by ectopic LMP1 expression, as determined by analyses of soft agar foci and tumor size in nude mice. Further, elevated LMPIP expression was also noted in cytoplasm and nuclei in EBVinfected NPC tumor cell mass and non-EBV-infected tumor cell lines. These results suggested that LMPIP may have an important mediator role in EBV-mediated neoplasm and may serve as a new target for therapy of tumors induced by EBV infection.

show abstract

“…For example, well-described oncogenes such as Myc, Ras, and E2F1, which deliver strong mitogenic signals, have also been reported to cause cell death. 33,34 In addition, insulin-like growth factor, which is a well-known mitogenic and antiapoptotic factor for many cells, was proven to significantly inhibit DNA synthesis and cell proliferation in a human lung adenocarcinoma cell line, possibly via the sustained activation of AKT1 and the induction of p21. 35 Therefore, it is possible that the outcome of AKT1 activation may vary depending on the type of stimulus and the microenvironment, or activated AKT1 may direct signals in an organ (or tumor)-specific manner.…”

Section: Discussionmentioning

confidence: 99%

The expression of phospho-AKT1 and phospho-MTOR is associated with a favorable prognosis independent of PTEN expression in intrahepatic cholangiocarcinomas

Lee

Choi

et al. 2012

Modern Pathology

View full text Add to dashboard Cite

AKT1 signaling pathway is important for the regulation of protein synthesis and cell survival with implications in carcinogenesis. In this study, we explored the prognostic significance of AKT1 pathway in intrahepatic cholangiocarcinomas. We investigated the status of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), phosphorylated (p) AKT1 (p-AKT1), p-mammalian target of rapamycin (p-MTOR), p-p70 ribosomal protein S6 kinase (p-RPS6KB2) and p-eukaryotic initiation factor 4E-binding protein-1 (p-EIF4EBP1) in 101 intrahepatic cholangiocarcinomas by immunohistochemistry. Western blot analysis was performed to verify the expression levels of p-AKT1 and p-MTOR. The relationship of protein expression with clinicopathological data and the correlations of protein expression levels were explored. The overexpression of p-AKT1, p-MTOR, and PTEN was associated with a better survival in patients with intrahepatic cholangiocarcinoma (P ¼ 0.0137, 0.0194, and 0.0337, respectively). In a multivariate analysis, PTEN was an independent prognostic factor, and p-AKT1 showed tendency (P ¼ 0.032 and 0.051, respectively). The overexpression of p-MTOR was correlated with well-to-moderately differentiated tumors (Po0.001) and tumors without metastasis (P ¼ 0.046). Expression levels of the AKT1 signaling pathway proteins in this study showed positive correlations with each other, except for PTEN. Aberrant expressions of p-AKT1 and p-MTOR in intrahepatic cholangiocarcinoma were associated with a favorable prognosis, possibly in a PTEN-independent manner. Our results indicate that dysregulation of the AKT1 pathway may have an important role in the development of intrahepatic cholangiocarcinoma, but not necessarily in the progression of the disease.

show abstract

E2F1 and c-Myc Potentiate Apoptosis through Inhibition of NF-κB Activity that Facilitates MnSOD-Mediated ROS Elimination

Cited by 281 publications

References 37 publications

A redox cycle within the cell cycle: ring in the old with the new

A redox cycle within the cell cycle: ring in the old with the new

Functional interaction of Ugene and EBV infection mediates tumorigenic effects

The expression of phospho-AKT1 and phospho-MTOR is associated with a favorable prognosis independent of PTEN expression in intrahepatic cholangiocarcinomas

Contact Info

Product

Resources

About