TRIM65 and p53
TRIM65 and p53
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Tripartite motif containing 65 (TRIM65) is a protein that in humans is encoded by the TRIM65 gene.
p53 is an important target of Tripartite-motif protein family member 65 (TRIM65) in lung cancer cells.
Let's look at how TRIM65 affects p53:
TRIM65 binds to and inactivates p53
Through Western blot analysis, Li et al found that TRIM65 was pulled down by anti-Flag antibody only in the presence, but not in the absence of Flag-p53, indicating that TRIM65 is a p53-associated protein.
When TRIM65 was highly expressed, Li et al observed a decrease in the expression of p53 in a dose-dependent manner. p53 target genes, including p21 and PUMA, were also downregulated in response to TRIM65 overexpression. In contrast, when TRIM65 concentration was decreased, the expression of p53, p21 and PUMA all increased.
TRIM65 has Oncogenic Properties
TRIM65 was first thought of being a potential oncogene when Li et al found that TRIM65 was heavily expressed in sites of NSCLC( non-small cell lung carcinoma ). Upon analysis, they found that TRIM65 binds to the N-terminus of p53 tumor suppressor and thus competes with MDM2 for p53 binding as the site of p53 for TRIM65 binding overlaps with the domain for MDM2 binding. Additionally, they observed that a decrease in the concentration of TRIM65 reduced the growth of H1299 cells, which are cells that have a null/ineffective p53.
Combined together, this data shows that the over expression of TRIM65 can contribute to NSCLC.
Animesh Dali | DePauw University
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