Structure and Function of the Ankyrin Repeats in the SWi4/SWi6 Transcription Complex of Budding Yeast.

A large and diverse set of proteins have been identified as containing ankyrin repeats, including several proteins in which the ankyrin repeat motifs may play a role in tumor development. These include Bcl-3, int-3, TAN-i, and pi6. The BCL-3 gene encodes a member of the I kappa B family of proteins and rearrangements involving the ankyrin repeat region BCL-3 have been identified in B-cell chronic lymphocytic leukemias 14. Int-3, a mouse proto-oncogene, is a common insertion site for the Mouse Mammary Tumor Virus MMTV. Activation of the int-3 ankyrin repeat sequences by MMTV produces poorly differentiated adenocarcinoma of the mammary and salivary glands in mice 10. TAN-i, the human Notch homologue, was first described as a breakpoint region oft 7,9 gene rearrangements found in T-cell acute lymphoblastic leukemias. This rearrangement places the gene encoding the beta T-cell receptor adjacent to the ankyrin repeat motifs of TAN-i 5. p16 is the protein product of theMTSJ multiple tumor suppressor-i gene. It is composed of only a series of four ankyrin repeats and is one member of the cyclin dependent kinase inhibitor family of proteins. p16 can compete with cyclin D and displace the cyclin subunit from its kinase binding site, thereby inhibiting ji to S progression through the cell cycle. Mutations in p16 have been noted in a variety of human tumors and tumor cell lines, in addition, mutations have been found in the germline of families predisposed to melanoma 9.