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PTM for Histone; 1. acetylation (Lys) 2. ubiquitination (Lys) 3. phosphorylation (Ser) H2Ax when phosphorylate --> gammaH2Ax! nucleosome = histone (H2A,H2B,H3,H4) + 147 bp DNA wrapping around 8 octa-histone and being locked with H1 (shown in my drawing) For H2A subdivided to 3; H2A1-H2A2 (balance from the other two) H2Ax (2-25%) H2Az (10%) Ref; DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139 ( J Biol Chem.  1998 Mar 6;273(10):5858-68.)

Paper: RSPO3 antagonism inhibits growth and tumorigenicity in colorectal tumors harboring common Wnt pathway mutations doi: 10.1038/s41598-017-15704-y I would like to start with my rough drawing since it can help me recognize by heart now. The concept of this paper relies on Wnt signaling that contributes to the growth of colorectal tumors. Mutation of genes in Wnt pathway that related to CRC is beta-catenin, APC and RNF43 and these type of mutations are found 90% of CRC. My understanding, this paper points out the microenvironment supporting the tumor growth. Not only Wnt ligand but also R-spondin is the ligand that can activate the Wnt signaling pathway. Wnt binds to the Fz directly whereas R-spondin (RSPO) quantitatively control RNF43. RSPO binds to RNF43 which leads to proteasomal degradation, therefore, controlling the availability of Fz on the membrane. It was shown that RSPO3 antagonism worked effectively with RSPO gene fusion type (RSPO-PTPRK) in CRC...

Paper: Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma doi: 10.1073/pnas.1307218110. Epub 2013 Jul 11 I like the picture that the team showed the cytotoxicity assay toward PDAC cell lines by using Wnt secretion inhibitor; LGK974. LGK974 inhibits the wnt-secretion by inhibiting the enzyme called "porcupine" which add the palmitoleic acid to the wnt as an indispensable signal for its secretion. What I have learned in this publication is molecular subtyping is a very important procedure for the cancer treatment since each molecular subtype will differently response to the treatment. The main idea for this paper is that; 1. PDAC cell lines have a different molecular genotypic signature. 2. There is more than 1 factor that supporting the growth of PDAC cell lines. 3. The growth of RNF43 malfunctioned PDAC cell lines relies on the Wnt pathway (by understanding this characteristic, we can apply the wnt inhibitor to this patient...