Role of the multifunctional CDP/Cut/Cux homeodomain transcription factor in regulating differentiation, cell growth and development

CDP/Cux/Cut proteins are an evolutionarily conserved family of proteins con taining several DNA binding domains: one Cut home odomain and one, two or t hree Cut repeats. In Drosophila melanogaster. genetic studies indicated tha t Cut functions as a determinant of cell-type specification in several tiss ues, notably in the peripheral nervous system, the wing margin and the Malp ighian tubule. Moreover, Cut was found to be a target and an effector of th e Notch signaling pathway. In vertebrates. the same functions appear to be fulfilled by two cur-related genes with distinct patterns of expression. Cl oning of the cDNA for the CCAAT-displacement protein (CDP) revealed that it was the human homologue of Drosophila Cut. CDP was later found be the DNA binding protein of the previously characterized histone nuclear factor D (H iNF-D). CDP and its mouse counterpart, Cux, were also reported to interact with regulatory elements from a large number of genes, including matrix att achment regions (MARs. CDP/Cut proteins were found generally to function as transcriptional repressors, although a participation in transcriptional ac tivation is suggested by some data. Repression by CDP/Cut involves competit ion for binding site occupancy and active repression via the recruitment of a histone deacetylase activity. Various combinations of Cut repeats and th e Cut homeodomains can generate distinct DNA binding activities. These acti vities an elevated in proliferating cells and decrease during terminal diff erentiation. One activity, involving the Cut homeodomain, is upregulated in S phase. CDP/Cut function is regulated by several post-translational modif ication events including phosphorylation, dephosphorylation, and acetylatio n. The CUTL1 gene in human was mapped to 7q22, a chromosomal region that is frequently rearranged in various cancers. (C) 2001 Published by Elsevier S cience B.V. All rights reserved.