Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The scaffold protein XB130 regulates cell growth, survival, and migration. Yeast two-hybrid screening suggests that XB130 interacts with another scaffold protein, Tks5. We hypothesized that XB130 and Tks5 form a macromolecular complex to mediate signal transduction cascades for the regulation of cell growth and survival. Coimmunoprecipitation demonstrated that XB130 and Tks5 interact endogenously and form a complex with Src tyrosine kinase. Structure-function studies showed that the fifth SH3 domain of Tks5 binds to the N-terminus of XB130, which contains polyproline-rich motifs. Cell growth and survival studies revealed that down-regulation of XB130 and/or Tks5 reduced cell proliferation, resulting in cell cycle inhibition at the G1 phase and increased caspase 3 activity and apoptosis. Moreover, cell proliferation and survival were increased by overexpression of XB130 or Tks5 but decreased when XB130/Tks5 binding was disrupted by overexpression of XB130 N-terminal deleted mutant and/or Tks5 fifth SH3 domain W1108A mutant. Furthermore, down-regulation of XB130 and/or Tks5 inhibited serum- and growth factor-induced Src activation and downstream phosphorylation of PI3K and Akt. Our results suggest that Tks5, similar to XB130, plays a role in cell proliferation and cell survival and that the interaction between XB130 and Tks5 appears to be critical for regulation of Src-mediated cellular homeostasis.
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PMID:XB130/Tks5 scaffold protein interaction regulates Src-mediated cell proliferation and survival. 2644 40

BACKGROUND The actin filament-associated protein (AFAP) family consists of 3 novel adaptor proteins: AFAP1, AFAP1L1, and AFAP1L2/XB130. Although evidence shows that AFAP1 and AFAP1L2 play an oncogenic role, the effect of AFAP1L1 on tumor cell behavior has not been fully elucidated, and it remains unknown whether AFAP1L1 could be a prognostic marker and/or therapeutic target of lung cancer. MATERIAL AND METHODS Human A549 non-small cell lung cancer (NSCLC) cells were used in this study. AFAP1L1 gene was knocked down by AFAP1L1 short hairpin RNA (shRNA) transfection. Cell proliferation was analyzed using Celigo image cytometry and MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay, cell cycle progression was assessed with flow cytometry, and cell apoptosis was determined by flow cytometry after annexin-n staining. The PathScan intracellular signaling array was used to investigate cancer-related signaling proteins influenced by knocking down AFAP1L1 in A549. RESULTS AFAP1L1 gene expression was successfully inhibited by the AFAP1L1-shRNA transfection. Cell proliferation was inhibited and cell proportions in G1 and G2/M phases were increased, and cell apoptosis was increased in the AFAP1L1-shRNA transfected cells as compared with negative control shRNA transfected cells. Using the PathScan intracellular signaling array, we found that downregulation of AFAP1L1 significantly activated P38 and caspase 3, and inhibited PRAS40 activation. CONCLUSIONS Our data show that AFAP1L1 promotes cell proliferation, accelerates cell cycle progression, and prevents cell apoptosis in lung cancer cells. Therefore, AFAP1L1 might play an oncogenic role in NSCLC.
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PMID:Actin Filament-Associated Protein 1-Like 1 Mediates Proliferation and Survival in Non-Small Cell Lung Cancer Cells. 2932 1