Signaling protein signature predicts clinical outcome of non-small-cell lung cancer.

Background: Non-small-cell lung cancer (NSCLC) is characterized by abnormalities of numerous signaling proteins that play pivotal roles in cancer development and progression. Many of these proteins have been reported to be correlated with clinical outcomes of NSCLC. However, none of them could provide adequate accuracy of prognosis prediction in clinical application.

Dysregulation of the miR-324-5p-CUEDC2 axis leads to macrophage dysfunction and is associated with colon cancer.

CUEDC2, a CUE-domain-containing protein, modulates inflammation, but its involvement in tumorigenesis is still poorly understood. Here, we report that CUEDC2 is a key regulator of macrophage function and critical for protection against colitis-associated tumorigenesis. CUEDC2 expression is dramatically upregulated during macrophage differentiation, and CUEDC2 deficiency results in excessive production of proinflammatory cytokines.

[Effects of knocking down Gankyrin on breast cancer metastasis in mice].

Objective: To establish Gankyrin knocking down 4T1-luc cell model and detect the effects of Gankyrin expression on breast cancer metastasis.

Methods: 4T1-luc cells carrying shGankyrin construct were established by lentivirus infection and antibiotic screening. Western blotting and real-time PCR were used to check the expression levels of Gankyrin.

Phosphorylation-triggered CUEDC2 degradation promotes UV-induced G1 arrest through APC/C(Cdh1) regulation.

DNA damage triggers cell cycle arrest to provide a time window for DNA repair. Failure of arrest could lead to genomic instability and tumorigenesis. DNA damage-induced G1 arrest is generally achieved by the accumulation of Cyclin-dependent kinase inhibitor 1 (p21).

CUEDC2 (CUE domain-containing 2) and SOCS3 (suppressors of cytokine signaling 3) cooperate to negatively regulate Janus kinase 1/signal transducers and activators of transcription 3 signaling.

Janus kinase 1/signal transducers and activators of transcription 3 (JAK1/STAT3) pathway is one of the recognized oncogenic signaling pathways that frequently overactivated in a variety of human tumors. Despite rapid progress in elucidating the molecular mechanisms of activation of JAK/STAT pathway, the processes that regulate JAK/STAT deactivation need to be further clarified. Here we demonstrate that CUE domain-containing 2 (CUEDC2) inhibits cytokine-induced phosphorylation of JAK1 and STAT3 and the subsequent STAT3 transcriptional activity.

Gankyrin plays an essential role in Ras-induced tumorigenesis through regulation of the RhoA/ROCK pathway in mammalian cells.

Activating mutations in Ras proteins are present in about 30% of human cancers. Despite tremendous progress in the study of Ras oncogenes, many aspects of the molecular mechanisms underlying Ras-induced tumorigenesis remain unknown. Through proteomics analysis, we previously found that the protein Gankyrin, a known oncoprotein in hepatocellular carcinoma, was upregulated during Ras-mediated transformation, although the functional consequences of this were not clear.

Identification of ubiquitin target proteins using cell-based arrays.

A global understanding of ubiquitinated proteins in vivo is key to unraveling the biological significance of ubiquitination. There are, however, a few effective screening methods for rapid analysis of ubiquitinated proteins. In the current study, we designed a cell-based cDNA expression array combined with cell imaging for the rapid identification of polyubiquitinated proteins, which normally accumulate to form the unique "dot" structure following inhibition of ubiquitin proteasomes.

CUE domain containing 2 regulates degradation of progesterone receptor by ubiquitin-proteasome.

Accumulated evidence indicates that progesterone receptors (PR) are involved in proliferation of breast cancer cells and are implicated in the development of breast cancer. In this paper, a yeast two-hybrid screen for PR led to the identification of CUE domain containing 2 (CUEDC2), whose function is unknown. Our results demonstrate that CUEDC2 interacts with PR and promotes progesterone-induced PR degradation by the ubiquitin-proteasome pathway.

Proteomics analysis reveals insight into the mechanism of H-Ras-mediated transformation.

We implemented a proteomics approach to the systematical analysis of the alterations in the proteome of NIH3T3 cells transformed by oncogenic H-RasV12. Forty-four proteins associated with Ras-mediated transformation have been identified, and 28 proteins were not previously reported. RT-PCR analysis showed that approximately 44% of target proteins identified showed concomitant changes in mRNA abundance.

PIAS3 induction of PRB sumoylation represses PRB transactivation by destabilizing its retention in the nucleus.

Progesterone receptor (PR) plays a critical role in cell proliferation and differentiation, and its transcriptional activity is known to be modulated by cofactor proteins. In the present study, we demonstrated that in the presence of progesterone, protein inhibitor of activated STAT-3 (PIAS3) significantly inhibited the PR transcriptional activity and the expression of progesterone-responsive genes. Reduction of endogenous PIAS3 by PIAS3 small-interfering RNA enhanced PR transactivation in a ligand-dependent manner.

MDM2 interacts with and downregulates a sarcomeric protein, TCAP.

Recent reports have shown that MDM2 may attenuate hypertrophy of cardiac myocytes. However, mechanism of MDM2 involving in this process is unclear. In this study, we identified a novel specific MDM2-binding protein TCAP by the yeast two-hybrid screen.

Two-dimensional electrophoresis protein profiling as an analytical tool for human acute leukemia classification.

Two-dimensional electrophoresis (2-DE) was used to profile the proteins of leukemic cells from 61 cases of akute leukemia (AL) characterized by the French-American-British (FAB) classification. The differentially expressed protein spots were identified by matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and electrospray ionization-tandem MS (ESI-MS/MS). The distinct protein profiles (DPPs) of AL FAB subtypes were explored successfully, including acute myeloid leukemia (AML), its subtypes (M2, M3, and M5), and acute lymphoid leukemia (ALL), which were homogeneous within different samples of the same subgroup but clearly differed from all other subgroups.

Proteomic analysis of human acute leukemia cells: insight into their classification.

Purpose: French-American-British (FAB) classification of acute leukemia with genetic heterogeneity is important for treatment and prognosis. However, the distinct protein profiles that contribute to the subtypes and facilitate molecular definition of acute leukemia classification are still unclear.

Experimental Design: The proteins of leukemic cells from 61 cases of acute leukemia characterized by FAB classification were separated by two-dimensional electrophoresis, and the differentially expressed protein spots were identified by both matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS) and tandem electrospray ionization MS (ESI-MS/MS).

A novel eIF5A complex functions as a regulator of p53 and p53-dependent apoptosis.

Although eukaryotic translation initiation factor 5A (eIF5A) was originally designated as an "initiation factor," recent data have shown it to be also involved in apoptosis. However, the actual function of eIF5A in apoptosis is still unknown. In this study, we performed yeast two-hybrid screens to identify eIF5A-interacting proteins to help us understand the mechanisms of eIF5A.

[The effect of eIF-5A on the G1-S in cell cycle regulation].

Eukaryotic initiation factor 5A (eIF-5A) contains an unusual amino acid, hypusine, which is formed post-translationally. Although eIF-5A and its hypusine modification are essential for eukaryotic cell viability, the precise physiological function of it has remained elusive. The aim of the study is to investigate how hypusine formation modulate the proliferation, cell cycle and apoptosis in leukaemia cells.

Proteomic analysis of ubiquitin-proteasome effects: insight into the function of eukaryotic initiation factor 5A.

The global effect of ubiquitin-proteasome (UP) inhibitors on leukemic cell proteome was analysed. A total of 39 protein spots, affected by UP inhibitors, were identified, including 11 new apoptosis-associated proteins. They are involved in different cellular functions and four were associated with caspase-3 activation.

[Nano-ESI-MS/MS identification on apoptosis qssociated proteins induced by inhibiting ubiquitin-proteasome pathway].

CapLC-ESI-MS/MS and nano-ESI-MS/MS techniques were used to identify the apoptosis associated proteins induced by inhibiting the ubiquitin-proteasome pathway in Mo7e leukaemic cells. In 2-DE, spot H was found to initiate its overexpression at 2 h after the inhibition and reached its peak at 6 h. It was identified as Rho GDI beta protein after the tandem mass spectrum and after the sequence of its tryptic peptides were obtained by the ESI-MS/MS techniques.