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The putative tumour suppressor Fus-2 is an N-acetyltransferase
P Zegerman1, A J Bannister, T Kouzarides
1Wellcome/CRC Institute, Department of Pathology, Cambridge University, Tennis Court Road, Cambridge, CB2 1QR, UK.
Abstract:
Acetyltransferases are essential enzymes for a wide variety of cellular processes and mutations in acetyltransferase genes have been associated with the development of certain cancers. For this reason, we conducted a computerized sequence homology search for novel acetyltransferases. Here, we show that the putative tumour suppressor protein Fus-2 has homology to the catalytic domain of acetyltransferases. We demonstrate that Fus-2 can acetylate the N-terminus of proteins using a ping-pong mechanism and that it has a specificity for substrates. Consistent with other N-acetyltransferases, Fus-2 localizes to the cytoplasm, as shown by GFP-tag experiments. Since the Fus-2 gene maps to the chromosomal region 3p21.3, which contains at least one tumour suppressor gene, the N-acetyltransferase functions of Fus-2 may be relevant to its potential role in cancer.
Insights
Researchers identified the tumor suppressor protein Fus-2 as a novel N-acetyltransferase. This enzyme acetylates protein N-termini and may play a role in cancer development.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Acetyltransferases are crucial enzymes involved in cellular processes.
- Mutations in acetyltransferase genes are linked to cancer development.
- Novel acetyltransferases are sought for understanding cellular functions and disease.
Purpose of the Study:
- To identify novel acetyltransferases using sequence homology searches.
- To characterize the enzymatic activity and cellular localization of the putative tumor suppressor protein Fus-2.
- To investigate the potential role of Fus-2's N-acetyltransferase function in cancer.
Main Methods:
- Computerized sequence homology search for novel acetyltransferases.
- Biochemical assays to demonstrate Fus-2's N-acetyltransferase activity and substrate specificity.
- GFP-tagging experiments to determine Fus-2's subcellular localization.
Main Results:
- Fus-2 exhibits homology to the catalytic domain of acetyltransferases.
- Fus-2 demonstrates N-acetyltransferase activity on protein N-termini via a ping-pong mechanism.
- Fus-2 displays substrate specificity and localizes to the cytoplasm.
- The Fus-2 gene is located in a chromosomal region associated with tumor suppressor genes.
Conclusions:
- Fus-2 functions as an N-acetyltransferase with specific substrate preferences.
- Fus-2's cytoplasmic localization is consistent with known N-acetyltransferases.
- The N-acetyltransferase activity of Fus-2 may contribute to its role as a tumor suppressor in the 3p21.3 chromosomal region.
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