Up-regulation of PDCD4 in senescent human diploid fibroblasts

Kang, Minji; Ahn, Hye-Sung; Lee, Ji-Young; Matsuhashi, Sachiko; Park, Woong-Yang

doi:10.1016/s0006-291x(02)00264-4

Cited by 54 publications

(49 citation statements)

References 26 publications

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“…It is also identified as a correlate of induced apoptosis (Shibahara et al, 1995;Zhang and DuBois, 2001) and cellular senescence (Kang et al, 2002). In the present work, we now suggest Pdcd4 to suppress the invasion cascade of cultured colon cancer with two different models.…”

Section: Pdcd4 Regulates Invasion and U-par Expression Jh Leupold Et Alsupporting

confidence: 58%

“…The pdcd4 cDNA is identical to murine MA-3 and TIS genes (Shibahara et al, 1995;Onishi and Kizaki, 1996), and there is a high homology to the human genes H731 and 197/15 (Azzoni et al, 1998;Yoshinaga et al, 1999). The human gene is located at chromosome 10q24 (Soejima et al, 1999) and its expression has been reported, for example, in human interleukin 12 (IL-12)-induced natural killer (NK) and T cells (Azzoni et al, 1998), small duct epithelial cells of the normal mammary gland (Soejima et al, 1999;Yoshinaga et al, 1999), a growth-suppressed human neuroendocrine pancreatic carcinoma cells (Stalberg et al, 2001), normal human lung tissue (Chen et al, 2003), or senescent human fibroblasts (Kang et al, 2002). Pdcd4 has been suggested to be linked to the process of apoptosis in response to different inducers (Shibahara et al, 1995;Zhang and DuBois, 2001), and has been shown to be regulated by topoisomerase inhibitors (Onishi et al, 1998), COX-2 inhibitors (Zhang and DuBois, 2001), Myb (Schlichter et al, 2001) and Akt (Palamarchuk et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Tumor suppressor Pdcd4 inhibits invasion/intravasation and regulates urokinase receptor (u-PAR) gene expression via Sp-transcription factors

et al. 2007

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Section: Pdcd4 Regulates Invasion and U-par Expression Jh Leupold Et Alsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Tumor suppressor Pdcd4 inhibits invasion/intravasation and regulates urokinase receptor (u-PAR) gene expression via Sp-transcription factors

et al. 2007

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“…PDCD4 is widely expressed in human tissues (Azzoni et al, 1998;Yoshinaga et al, 1999;Kang et al, 2002;Chen et al, 2003) and several regulatory mechanisms of PDCD4 expression have been reported. Human PDCD4 (E) TGFb1 induced mitochondrial increase of Bax, cytosolic increase of cytochrome c, and changes in procaspase-8, -9, and -3 in Huh7 cells.…”

Section: Discussionmentioning

confidence: 99%

“…It was shown that the mouse Pdcd4-protein directly interacts with elF4A, blocking its binding to elF4G, and modulating protein translation by inhibiting the initiation of Cap-dependent translation (Yang et al, 2003b, Jansen et al, 2005. On the other hand, Kang et al (Kang et al, 2002) showed that the expression of human PDCD4 is related to cellular senescence and the PDCD4-protein interacted with elF4G and the ribosomal protein S13 (RPS 13). Moreover, expression of PDCD4 was regulated by the transcription factor myb in chicken systems (Schlichter et al, 2001a, b).…”

Section: Introductionmentioning

confidence: 99%

Involvement of programmed cell death 4 in transforming growth factor-β1-induced apoptosis in human hepatocellular carcinoma

et al. 2006

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The programmed cell death 4 (PDCD4) gene was originally identified as a tumor-related gene in humans and acts as a tumor-suppressor in mouse epidermal carcinoma cells. However, its function and regulatory mechanisms of expression in human cancer remain to be elucidated. We therefore investigated the expression of PDCD4 in human hepatocellular carcinoma (HCC) and the role of PDCD4 in human HCC cells. Downregulation of PDCD4 protein was observed in all HCC tissues tested compared with corresponding noncancerous liver, as revealed by Western blotting or immunohistochemical staining. Human HCC cell line, Huh7, transfected with PDCD4 cDNA showed nuclear fragmentation and DNA laddering characteristic of apoptotic cells associated with mitochondrial changes and caspase activation. Transforming growth factor-b1 (TGF-b1) treatment of Huh7 cells resulted in increased PDCD4 expression and occurrence of apoptosis, also concomitant with mitochondrial events and caspase activation. Transfection of Smad7, a known antagonist to TGF-b1 signaling, protected cells from TGF-b1-mediated apoptosis and suppressed TGF-b1-induced PDCD4 expression. Moreover, antisense PDCD4 transfectants were resistant to apoptosis induced by TGF-b1. In conclusion, these data suggest that PDCD4 is a proapoptotic molecule involved in TGF-b1-induced apoptosis in human HCC cells, and a possible tumor suppressor in hepatocarcinogenesis.

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“…The Pdcd4 protein has recently been shown to interact with eucaryotic translation initiation factors (eIFs) eIF4A and eIF4G (Go¨ke et al, 2002;Kang et al, 2002;Yang et al, 2003), suggesting that it might be involved in regulating protein translation. In support of this idea, Yang et al (2003) have localized the protein to the cytoplasm and have demonstrated that it inhibits the helicase activity of eIF4A and cap-dependent translation.…”

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confidence: 99%

The transformation suppressor protein Pdcd4 shuttles between nucleus and cytoplasm and binds RNA

et al. 2003

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The Pdcd4 gene has originally been isolated in a search for genes that are activated in cells undergoing apoptosis. Independent of these studies, the Pdcd4 gene has been implicated in the suppression of tumor-promoter-mediated transformation of keratinocytes and as a downstream target of Myb in hematopoietic cells. The Pdcd4 protein has weak homology to the eucaryotic translation initiation factor eIF4G and has been shown to interact with certain translation initiation factors. To explore the molecular function of the Pdcd4 protein, we have studied its subcellular localization. We show that the Pdcd4 protein is a predominantly nuclear protein under normal growth conditions and that it is exported from the nucleus by a leptomycin B-sensitive mechanism upon serum withdrawal. The protein contains two nuclear export signals, one of which is very potent. In addition, we demonstrate that the Pdcd4 protein has RNA-binding activity and that the sequences involved in RNA-binding are located in the amino-terminal part of the protein. Taken together, our data raise the possibility that Pdcd4 is involved in some aspect of nuclear RNA metabolism in addition to its suspected role in protein translation.

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Up-regulation of PDCD4 in senescent human diploid fibroblasts

Cited by 54 publications

References 26 publications

Tumor suppressor Pdcd4 inhibits invasion/intravasation and regulates urokinase receptor (u-PAR) gene expression via Sp-transcription factors

Tumor suppressor Pdcd4 inhibits invasion/intravasation and regulates urokinase receptor (u-PAR) gene expression via Sp-transcription factors

Involvement of programmed cell death 4 in transforming growth factor-β1-induced apoptosis in human hepatocellular carcinoma

The transformation suppressor protein Pdcd4 shuttles between nucleus and cytoplasm and binds RNA

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