Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/148163
Title: INVESTIGATING THE ROLES OF USP26 AND SHP2 IN THE REGULATION OF THE SMURF2-SMAD7-MEDIATED DOWNREGULATION OF THE TGF-β PATHWAY
Authors: LUI KIT LENG SARAH
ORCID iD:   orcid.org/0000-0002-4550-8145
Keywords: TGF-β, Deubiquitination, Cancer, USP26, SHP2, Phosphorylation
Issue Date: 4-Oct-2018
Citation: LUI KIT LENG SARAH (2018-10-04). INVESTIGATING THE ROLES OF USP26 AND SHP2 IN THE REGULATION OF THE SMURF2-SMAD7-MEDIATED DOWNREGULATION OF THE TGF-β PATHWAY. ScholarBank@NUS Repository.
Abstract: Transforming growth factor-β (TGF-β) signaling amplitude is tightly regulated to maintain appropriate physiological responses. A well-studied mechanism involves a negative feedback loop in which SMAD7, a direct transcriptional target of downstream TGF-β signals, acts as a scaffold protein recruiting the E3 ligase SMURF2 to target the TGF-β receptor complex for ubiquitin-mediated degradation. However, regulation of this SMURF2-SMAD7 complex by post-translational modifications, including ubiquitination and phosphorylation, remains poorly understood. Here I identify USP26 as a novel component of the TGF-β negative feedback loop, regulating ubiquitin-mediated SMAD7 turnover, leading to TGF-β receptor degradation. Clinically, loss of USP26 correlates with high TGF-β activity and poor prognosis in glioblastoma and breast cancer. I also identify that SHP2 dephosphorylates and activates SMURF2, leading to TGF-β receptor degradation. Interestingly, TGF-β signaling could decrease SHP2 protein levels, suggesting a novel feed-forward loop is present. The data therefore indicates USP26 and SHP2 as novel regulators of the pathway.
URI: http://scholarbank.nus.edu.sg/handle/10635/148163
Appears in Collections:Master's Theses (Open)

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