Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1832588 (PSS)
 2,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cellular prion protein (PrP) is a highly conserved, widely expressed, glycosylphosphatidylinositol-anchored (GPI-anchored) cell surface glycoprotein. Since its discovery, most studies on PrP have focused on its role in neurodegenerative prion diseases, whereas its function outside the nervous system remains unclear. Here, we report that human pancreatic ductal adenocarcinoma (PDAC) cell lines expressed PrP. However, the PrP was neither glycosylated nor GPI-anchored, existing as pro-PrP and retaining its GPI anchor peptide signal sequence (GPI-PSS). We also showed that the PrP GPI-PSS has a filamin A-binding (FLNa-binding) motif and interacted with FLNa, an actin-associated protein that integrates cell mechanics and signaling. Binding of pro-PrP to FLNa disrupted cytoskeletal organization. Inhibition of PrP expression by shRNA in the PDAC cell lines altered the cytoskeleton and expression of multiple signaling proteins; it also reduced cellular proliferation and invasiveness in vitro as well as tumor growth in vivo. A subgroup of human patients with pancreatic cancer was found to have tumors that expressed pro-PrP. Most importantly, PrP expression in tumors correlated with a marked decrease in patient survival. We propose that binding of pro-PrP to FLNa perturbs FLNa function, thus contributing to the aggressiveness of PDAC. Prevention of this interaction could provide an attractive target for therapeutic intervention in human PDAC.
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PMID:Binding of pro-prion to filamin A disrupts cytoskeleton and correlates with poor prognosis in pancreatic cancer. 1969 Mar 85

By using "our devised up-to-the-second technique" over 30 years ago, we succeeded in the first isolation in the world of the three different kinds of mammalian cell mutants defective in the biosynthesis on each of phosphatidylserine (PS), cardiolipin (CL) and sphingomyelin (SM) from the parental CHO cells. As the results, we found that during the biosyntheses of PS and SM, the biosynthetic precursor or the final lipids are transported from their synthesized intracellular organelles to the plasma membranes via the other intracellular organelles. We further clarified the presence of the reversed routes for PS and SM from the plasma membranes to their synthesized organelles too. Our first epoch-making finding is not only the cycling inter-conversion reactions between PS and PE catalyzed by PSS-II and PSD but also their simultaneous transferring between MAM and Mit (found by O. Kuge). Our second finding is "the ceramide-trafficking protein (CERT)" working as the specific transfer protein of ceramide from the ER to the Golgi apparatus, during the SM biosynthesis (by K. Hanada). As for their new biological roles, we clarified possible contribution of PS and/or PE to the fusion process between viral envelope and endosomal membrane, releasing the genetic information of the virus to the host cytoplasm. CL is contributing to the functional NADH-ubiquinone reductase activity by keeping the right structure of Coenzyme Q9 for its functioning. SM and cholesterol form the microdomain within the plasma membrane, so-called "the raft structure" where the GPI-anchored proteins are specifically located for their functioning.
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PMID:Reminiscence of our research on membrane phospholipids in mammalian cells by using the novel technology. 2322 49