My note on paper: RNF43 interacts with NEDL1 and regulates p53-mediated transcription

Paper: RNF43 interacts with NEDL1 and regulates p53-mediated transcription
(doi: 10.1016/j.bbrc.2010.11.082)

Abstract part:
1.ubiquitination proteasome is involved with oncogenesis in colon
2.stability of b-catenin (oncogene for colon carcinoma) is degraded by ubiquitin system
3.RNF43 is highly expressed and promote cell growth

Gap:
The role of RNF43 in carcinogenesis is not clear

Result:
-Using yeast two hybrid identify NEDD-4-like ubiquitin-protein ligase-1 (NEDL1) which bind to the RNF43
-Binding - enhance pro-apoptotic activity by p53
- RNF43 interacts with p53;
     *  suppress the TF activity in H1299 Cell (cells have a homozygous partial deletion of the p53 protein -- making the cell proliferate indefinitely)
     *  reduce apoptosis induced by UV
-RNF43 is associated with p53-mediated apoptosis with collaboration of NEDL1 in colorectal carcinogenesis


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Intro:
1.Cytotoxic of most chemotherapeutic drugs is often mediated by activation of apoptotic pathways
2.Altered expression of genes encoding apoptotic proteins may produce drug resistance
3.p53 plays role in cell cycle arrest + apoptosis
4.p53 is regulated by diverse kind of modifications; phosphorylation, acetylation and ubiquitination


Method:
Cell lines:
HEK293T (hypotriploid human cell line)
HCT116  (colon cell line)
H1299 (no expression of p53)

Human RNF43 was amplified by RT-PCR from the colon cancer cell line SW480

Result and Discussion:

p53 function as:

1. cell cycle arrest to initiate DNA repair

2. undergo apoptosis

RNF43 -

1.suppress apoptosis by either UV or CDDP treatment

2. RNF43 regulate cell growth and apoptosis via NEDL1+p53

3. function as negative regulator of NEDL1

p53 is ubiquitinated by Mdm2

Acetylation of p53 - disrupt the interaction between p53-Mdm2

unclear:

1.Interaction of RNF43 with NEDL1 and p53 - cause what type of post-modification toward p53

(high NEDL1 support TF activity of p53 (not relate to proteasome degradation); RNF43 interacts with NEDL1+p53 - reduce TF activity

2. using KO mice - will clear the carcinogenesis in colorectal region