Structural insights into Gemin5-guided selection of pre-snRNAs for snRNP assembly.

In cytoplasm, the survival of motor neuron (SMN) complex delivers pre-small nuclear RNAs (pre-snRNAs) to the heptameric Sm ring for the assembly of the ring complex on pre-snRNAs at the conserved Sm site [A(U)G]. Gemin5, a WD40 protein component of the SMN complex, is responsible for recognizing pre-snRNAs. In addition, Gemin5 has been reported to specifically bind to the mG cap.

Activation of various downstream signaling molecules by IGFBP-3.

Insulin-like growth factor binding protein-3 (IGFBP-3), a secretory protein, is the most abundant IGF binding protein present in human serum among all IGF binding proteins. IGFBP-3 shows decreased level of expression in cancerous cells but has been known to be present in significant amounts in normal or non-cancerous cells. IGFBP-3 can induce apoptosis in prostate cancer cells either in an IGF-dependent manner or independently of IGF binding.

Signal Transduction Pathways Mediated by Secreted and Non-secreted Forms of intact Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) and its 1-97 N-terminal Fragment in PC-3 Human Prostate Cancer Cells.

Our previous results indicated that both the secreted and the intracellular form of full length and 1-97 N-terminal fragment of IGFBP-3 induces apoptosis in PC-3 human prostate cancer cells in an IGF-dependent and independent manner. This study was undertaken to delineate possible down-stream signaling pathways that are involved in this process. Intact IGFBP-3 and its N-terminal 1-97 fragments with or without a signal pro-peptide was fused to YFP and expressed in PC-3 human prostate cancer cells.

The effect of a novel frizzled 8-related antiproliferative factor on in vitro carcinoma and melanoma cell proliferation and invasion.

Antiproliferative factor (APF) is a potent frizzled protein 8-related sialoglycopeptide inhibitor of bladder epithelial cell proliferation that mediates its activity by binding to cytoskeletal associated protein 4 in the cell membrane. Synthetic asialylated APF (as-APF) (Galβ1-3GalNAcα-O-TVPAAVVVA) was previously shown to inhibit both normal bladder epithelial as well as T24 bladder carcinoma cell proliferation and heparin-binding epidermal growth factor-like growth factor (HB-EGF) production at low nanomolar concentrations, and an L: -pipecolic acid derivative (Galβ1-3GalNAcα-O-TV-pipecolic acid-AAVVVA) was also shown to inhibit normal bladder epithelial cell proliferation. To better determine their spectrum of activity, we measured the effects of these APF derivatives on the proliferation of cells derived from additional urologic carcinomas (bladder and kidney), non-urologic carcinomas (ovary, lung, colon, pancreas, and breast), and melanomas using a (3)H-thymidine incorporation assay.

Antiproliferative factor decreases Akt phosphorylation and alters gene expression via CKAP4 in T24 bladder carcinoma cells.

Background: Urinary bladder cancer is a common malignancy worldwide, and outcomes for patients with advanced bladder cancer remain poor. Antiproliferative factor (APF) is a potent glycopeptide inhibitor of epithelial cell proliferation that was discovered in the urine of patients with interstitial cystitis, a disorder with bladder epithelial thinning and ulceration. APF mediates its antiproliferative activity in primary normal bladder epithelial cells via cytoskeletal associated protein 4 (CKAP4).