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Molecular and Cellular Biology, September 2001, p. 6332-6345, Vol. 21, No. 18
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.18.6332-6345.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

S Phase-Specific Proteolytic Cleavage Is Required To Activate Stable DNA Binding by the CDP/Cut Homeodomain Protein

Nam Sung Moon,1,2 Peter Premdas,1 Mary Truscott,1 Lam Leduy,1 Ginette Bérubé,1 and Alain Nepveu1,2,3,4,*

Molecular Oncology Group, McGill University Health Center,1 and Departments of Biochemistry,2 Medicine,3 and Oncology,4 McGill University, Montreal, Quebec, Canada H3A 1A1

Received 14 May 2001/Accepted 13 June 2001

The CCAAT displacement protein (CDP), the homologue of the Drosophila melanogaster Cut protein, contains four DNA binding domains that function in pairs. Cooperation between Cut repeat 3 and the Cut homeodomain allows stable DNA binding to the ATCGAT motif, an activity previously shown to be upregulated in S phase. Here we showed that the full-length CDP/Cut protein is incapable of stable DNA binding and that the ATCGAT binding activity present in cells involves a 110-kDa carboxy-terminal peptide of CDP/Cut. A vector expressing CDP/Cut with Myc and hemagglutinin epitope tags at either end generated N- and C-terminal products of 90 and 110 kDa, suggesting that proteolytic cleavage was involved. In vivo pulse/chase labeling experiments confirmed that the 110-kDa protein was derived from the full-length CDP/Cut protein. Proteolytic processing was weak or not detectable in G0 and G1 but increased in populations of cells enriched in S phase, and the appearance of the 110-kDa protein coincided with the increase in ATCGAT DNA binding. Interestingly, the amino-truncated and the full-length CDP/Cut isoforms exhibited different transcriptional properties in a reporter assay. We conclude that proteolytic processing of CDP/Cut at the G1/S transition generates a CDP/Cut isoform with distinct DNA binding and transcriptional activities. These findings, together with the cleavage of the Scc1 protein at mitosis, suggest that site-specific proteolysis may play an important role in the regulation of cell cycle progression.

* Corresponding author. Mailing address: Molecular Oncology Group, McGill University Health Center, 687 Pine Ave. West, Montreal, Quebec H3A 1A1, Canada. Phone: (514) 842-1231 ext. 5842. Fax: (514) 843-1478. E-mail: alain{at}lan1.molonc.mcgill.ca.

Molecular and Cellular Biology, September 2001, p. 6332-6345, Vol. 21, No. 18
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.18.6332-6345.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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