UMass Chan AffiliationsDepartment of Biochemistry and Molecular Pharmacology
Document TypeJournal Article
Cell Line, Tumor
Drug Delivery Systems
N-Terminal Acetyltransferase A
N-Terminal Acetyltransferase E
cell cycle arrest
Enzymes and Coenzymes
MetadataShow full item record
AbstractEvasion of apoptosis and active cell proliferation are among the characteristics of cancer cells. Triggering the induction of apoptosis or reducing the proliferative rate will potentially be helpful for cancer treatment. Recently, several reports demonstrated that knockdown of the protein acetyltransferase hARD1 significantly reduced the growth rate of human cancer cell lines. Furthermore, hARD1 knockdown induced apoptosis or sensitized cells to drug induced apoptosis. hARD1 acts in complex with the NATH protein and catalyzes cotranslational acetylation of protein N-termini. Thus, it was suggested that the effects on cell proliferation and apoptosis induction are due to a reduced level of N-terminal acetylation of certain substrate proteins. NATH was originally identified as upregulated in thyroid papillary carcinomas and has lately also been found to correlate with aggressiveness and differentiation status of neuroblastic tumours. On the other hand, researchers recently reported that hARD1 acetylates Beta-catenin. Knockdown of hARD1 reduced the transcriptional activity of the Beta-Catenin/TCF4 complex, downregulating cyclin D1 and thereby promoting G1-arrest and inhibition of cell proliferation of lung cancer cells. Although the underlying molecular mechanisms need further clarification, several reports suggest that reduction of hARD1 negatively affects cell growth. Thus, hARD1 or the hARD1-NATH complex stands out as attractive drug targets in cancer treatment. One challenge will be to develop specific inhibitors that discriminate between hARD1 and the many other enzymes, including the histone acetyltransferases, using acetyl-coenzyme A as acetyl donor. This review focuses on the enzymatic and biological activities of hARD1, and potential mechanisms of functional inhibition.
SourceCurr Cancer Drug Targets. 2008 Nov;8(7):545-53. doi:10.2174/156800908786241113
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/50057
At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.
Related ResourcesLink to Article in PubMed