The expression and function of TRIM28 in hepatocellular carcinoma and the characterization of phospho-S681 and phospho-S757 polyclonal antibodies
Date Issued
2010
Date
2010
Author(s)
Wang, Chih-Ta
Abstract
TRIM28 (tripartite motif protein 28) is a corepressor for large family of Krüpple-associated box domain containing zinc finger transcription factors and coordinates KRAB-mediated transcription repression by recruitment of HP1 (heterochromatin protein1), histone methyltransferase SETDB1, and two chromatin-remodeling and histone deacetylation complexes N-CoR1 and NuRD. TRIM28-mediated repression complexes and heterochromatin formation are tightly coordinated leading to silencing of genes. Moreover, it was also reported that TRIM28 is essential for cell proliferation, differentiation and early embryonic development in mice. To study the relationship between the expression of TRIM28 and the growth and invasiveness of hepatocellular carcinoma (HCC), I performed immunohistochemical staining of clinical specimens. TRIM28 is overexpressed in HCC and is likely to involve in its abnormal growth characteristics. Post-translational modifications have important functional impacts on TRIM28. For example, phosphorylation of TRIM28/S824 was shown to be involved in DNA-damaged response while phosphorylation at S473 modulates its interaction with HP1 to differentially regulate cell cycle-related genes. Recently, the phosphorylation of S681 and S757 were identified in HeLa cells, but their functions remain unknown. We generated polyclonal antibodies against phosphorylated TRIM28/Ser681 and Ser757. These phosphorylation events appeared at prometaphase of HeLa cells. Similar to wild type TRIM28, S681A mutant dissociates from condensed chromosomes in prophase and re-associates with chromatin in anaphase. The potential function of phospho-S681 is discussed. The phosphorylation of S757 was completely abolished after Roscovitine treatment. It is likely that Cdk1 is responsible for the phosphorylation of S757.
Subjects
HCC
phosphorylation
prometaphase
Type
thesis
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