Pim-1 Kinase-Dependent Phosphorylation of p21Cip1/WAF1 Regulates Its Stability and Cellular Localization in H1299 Cells

Zhang, Yandong; Wang, Zeping; Magnuson, Nancy S.

doi:10.1158/1541-7786.mcr-06-0388

Cited by 113 publications

(114 citation statements)

References 58 publications

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…The knockdown efficiency correlated with the strength of the inhibitory effect on cell proliferation ('gene dose effect,' see Figures 3, 4 and 7). Thus, these results confirm previous studies, which had shown that the reduction of endogenous Pim-1 levels by RNAi negatively affects the proliferation capacity of the human lung carcinoma cell line H1299, of the prostate cancer cell line PC-3 and of K562 cells (Zhang et al, 2007(Zhang et al, , 2008(Zhang et al, , 2010.…”

Section: Discussionsupporting

confidence: 92%

The proto-oncogene Pim-1 is a target of miR-33a

et al. 2011

View full text Add to dashboard Cite

The constitutively active serine/threonine kinase Pim-1 is upregulated in different cancer types, mainly based on the action of several interleukines and growth factors at the transcriptional level. So far, a regulation of oncogenic Pim-1 by microRNAs (miRNAs) has not been reported. Here, we newly establish miR-33a as a miRNA with potential tumor suppressor activity, acting through inhibition of Pim-1. A screen for miRNA expression in K562 lymphoma, LS174T colon carcinoma and several other cell lines revealed generally low endogenous miR33a levels relative to other miRNAs. Transfection of K562 and LS174T cells with a miR-33a mimic reduced Pim-1 levels substantially. In contrast, the cell-cycle regulator cyclin-dependent kinase 6 predicted to be a conserved miR-33a target, was not downregulated by the miR-33a mimic. Seed mutagenesis of the Pim-1 3 0 -untranslated region in a luciferase reporter construct and in a Pim-1 cDNA expressed in Pim-1-deficient Skov-3 cells demonstrated specific and direct downregulation of Pim-1 by the miR-33a mimic. The persistence of this effect was comparable to that of a small interfering RNA-mediated knockdown of Pim-1, resulting in decelerated cell proliferation. In conclusion, we demonstrate the potential of miR-33a to act as a tumor suppressor miRNA, which suggests miR-33a replacement therapy through delivery of miR mimics as a novel therapeutic strategy.

show abstract

Section: Discussionsupporting

confidence: 92%

The proto-oncogene Pim-1 is a target of miR-33a

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Consistent with these observations, ablation of TCTP decreased Pim-3 expression and the amounts of phosphorylated p21, the molecules that participate in cell progression at G 0 -G 1 phase at the tumor sites in the injected mice (ref. 27; Fig. 4I).…”

Section: Ablation Of Tctp Protein Prevents Pim-3-mediated Tumor Growtmentioning

confidence: 94%

A Novel Regulatory Mechanism of Pim-3 Kinase Stability and Its Involvement in Pancreatic Cancer Progression

Zhang

Liu

Wang

et al. 2013

Molecular Cancer Research

View full text Add to dashboard Cite

Translationally controlled tumor protein (TCTP/TPT1) was identified from a yeast 2-hybrid screen and shown to interact with Pim-3, a member of the proto-oncogene Pim family with serine/threonine kinase activity. TCTP was aberrantly expressed in human pancreatic cancer cells and malignant ductal epithelial cells, but not in normal pancreatic duct epithelial cells adjacent to tumor foci of human pancreatic cancer tissue. Moreover, TCTP colocalized with Pim-3 both in human pancreatic cancer cells and in clinical tissues. Mapping studies revealed that the interaction between Pim-3 and TCTP occurred through the C-terminal region of Pim-3 and N-terminal region of TCTP. Although Pim-3 had no effect on TCTP expression or phosphorylation, overexpression of TCTP increased the amount of Pim-3 in a dose-dependent manner. Interestingly, RNAi-mediated ablation of TCTP expression reduced Pim-3 protein but not mRNA, through a mechanism involving the ubiquitin-proteasome degradation system. As a consequence of Pim-3 instability and subsequent degradation, tumor growth in vitro and in vivo was inhibited by arresting cell-cycle progression and enhancing apoptosis. Furthermore, TCTP and Pim-3 expression were significantly correlated in pancreatic adenocarcinoma specimens, and patients with highly expressed TCTP and Pim-3 presented with a more advanced tumor stage. These observations indicate that TCTP enhances Pim-3 stability to simultaneously promote and prevent cell-cycle progression and apoptosis, respectively. Hence, TCTP and Pim-3 serve a pivotal role in human pancreatic cancer with important ramifications for clinical diagnostic and therapeutic implications.

show abstract

“…Interestingly, both CXCL12-CXCR4 and EGF-EGFR lead to activation of the JAK-STAT signaling pathway, which regulates PIM1 expression (Soriano et al, 2003), whereas PMA treatment is also known to produce a rapid induction of PIM1 expression (Wingett et al, 1996). As some of the PIM1 target sites, like the apoptosis regulator BAD (Ser112) or the cell cycle regulator p21 (WAF1) (Thr145/Ser146), are also phosphorylated by other protein kinases, such as RAF1, PAK5, RSK2/5 for the former and PKC- or AKT for the latter (Aho et al, 2004;Jin et al, 2005;Kim et al, 2006, Oh et al, 2006Zhang et al, 2007), it is unlikely that PIM1 is the only kinase that phosphorylates CXCR4-Ser339. Although the exact mechanisms remain to be elucidated, based on our results, PIM1-regulated phosphorylation of CXCR4-S339 could provide an interaction platform for proteins that regulate receptor surface reexon December 15, 2015 jem.rupress.org…”

Section: Methodsmentioning

confidence: 99%