Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/50864
Title: Characterization of pellino1 and pellino2 in toll-like receptor signaling
Authors: Dai, Liang
Keywords: DRNTU::Science::Biological sciences::Biochemistry
Issue Date: 2012
Publisher: Nanyang Technological University
Source: Dai, L. (2012). Characterization of pellino1 and pellino2 in toll-like receptor signaling. Doctoral thesis, Nanyang Technological University, Singapore.
Abstract: Pellino family proteins were first identified as interacting partners with kinase IRAK1 in TLR/IL-1R pathway. There are three Pellino isoforms in human cells, termed Pellino1, Pellino2 and Pellino3. They contain a FHA and a RING domain in the N- and C-terminus regions respectively. The major variances among the isoforms reside in their N-terminus regions, as with an extended stretch found only in Pellino3. In the first part of my study, I have characterized Pellino2 and Pellino1 in the context of TLR signaling. I have found IRAK1 phosphorylates and activates Pellino2 through Ser-137 site on Pellino2. In return, activated Pellino2 synthesizes K27 linked poly-ubiquitin chains on IRAK1. I have also found endogenous Pellino1 is induced by TLR3 and TLR4 ligands (e.g. Poly (I:C) and LPS, respectively). The induction of Pellino1 is TRIF pathway dependent and plays a negative role on the production of selective cytokines. In the second part of my study, I have identified a group of Pellino1 interacting partners in HEK293 cells by LC-MS/MS. These interacting proteins are mainly involved in DNA damage response revealing a novel function of Pellino1 in DNA damage signaling. This hypothesis has been validated by the recruitment of Pellino1 to DNA damage sites mediated through its FHA domain and one uncharacterized NLS present in its N-terminus. Moreover, the interaction between Pellino1 and p53 (one of the interacting proteins identified in this project) has been validated in endogenous level. By biochemical approach, it is suggested Pellino1 preferentially binds to Thr-18 phosphorylated p53 through its FHA domain. Therefore, such interaction is enhanced during DNA damage response. Further study is needed to elucidate the functional role of Pellinos family proteins in DNA damage response pathway.
URI: http://hdl.handle.net/10356/50864
DOI: 10.32657/10356/50864
Schools: School of Biological Sciences 
Rights: This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Theses

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