Random Records

Note: The Unusual Case of Porcupine (doi:10.1126/science.1228179) Forward chemical genetics: Know the target of the chemical compound -- screening for the phenotype in cells Reverse chemical genetics: Know the protein target -- screening for the action of the chemical compound Wnt proteins is pivotal in animal development and tissue homeostasis, and has become a high-priority anticancer drug target given its essential role in colorectal cancer and its contribution to a broad range of other cancer types. Roel Nusse, Varmus linked deviant activity of Wnt molecules to cancer. LGK974—an acyltransferase called Porcupine (Porcn) that adds fatty acid to Wnt—has been well studied, few of the meeting participants were aware of the drug candidate. Discovered in screens for genes that affect embryonic patterning in the fruit fly, PORCN is the founding member of a 16-gene family with predicted acyltransferase activity. The fatty acyl modification of Wnt, Hedgehog, and...

Note for: Molecular Role of RNF43 in Canonical and Noncanonical Wnt Signaling (doi: 10.1128/MCB.00159-15) It is a bit hard to follow when reading this paper. Wnt1 class-- canonical Wnt go through beta-catenin Degradation complex includes; 1.adenomatous polyposis coli (APC) 2.axin 3.casein kinase Ialpha (CKIalpha) 4.glycogen synthase kinase 3beta (GSK-3beta) No Wnt-stimulant --> beta catenin is phosphorylated by degradation cpx leading to degradation by ubiquitin proteasome system by interact through SCFbetaTrCP ubiquitin ligase Finalized Wnt-catenin activation --> produce c-Myc which maintains undifferentiated state of cells. Wnt5a class-- non-canonical Wnt 1.not cause accumulation of beta-catenin and no induction of target genes 2.involve in cell polarity and cell migration+antagonizes Wnt/beta-catenin -- play role as tumor suppressor RNF43 suppresses both canonical and non-canonical but in different manner -- The research quest...

Paper: RNF43 (doi: 10.1136/jclinpath-2017-204763) Gene of the month in the journal of clinical pathology Only point out the detail I am interested Abstract; RNF43 1.function as tumor suppressor 2.negative feedback to wnt/beta-catenin 3.no RNF43 - no degradation of Frizzled and enhance the wnt/b-catenin signaling pw Introduction part; ZNRF3 -- Zinc And Ring Finger 3 --moderate identity 39% with RNF43 Profile Human RNF43; chromosome 17q23.2 11 exons - spanning 60 kb RNF43 proteins -- 2 isoforms 1. isoform 1 has 2 variants (shorter and longer) - different in mRNA strands but encoding the same protein 2. isoform 2 has shorter N-ter compare to isoform1 3. 783AA -- 90kDa RNF43 protein domains; 1. signal peptide 2. PA - protease-associated domain 2.1 PA -- putative protein recognition domain in distinctive set of TM ubiquitin ligase 2.2 function endocytic pw and cell surface PA domain of RN43 requires Dishevelled as adaptor to bind with Friz...