Elucidating the Role of cAb1 and the Abi-Family of cAB1 Target Proteins in Cancer Development and Progression
Abstract
Abi-interactor (Abi) proteins bind and are phosphorylated by the non-receptor tyrosine kinases Abi and Arg. Two Abi family genes, Abi-1 and Abi-2, have been identified. Abi proteins demonstrate properties consistent with a potential tumor suppressor function. We investigated the role of Abi-l and Abi-2 proteins and their interactions with c-Abl and c- Abl-derived oncogenes in normal development and tumorigenesis. Abi-l and Abi-2 exhibit both unique and overlapping temporal-spatial patterns of expression during embryonic and post-natal mouse development. Abi-2 is enriched in regions of the central and peripheral nervous systems (CNS and PNS) pre- and post-natally. Abi-l is also enriched in regions of the post-natal brain, but is not enriched in the pre-natal CNS and is absent from examined PNS structures. Abi proteins undergo changes in phosphorylation during development. Examination of Abi proteins in the presence of oncogenic forms of Abl and Src revealed loss of Abi expression due to ubiquitin-mediated degradation. Abi proteins were down- regulated or exhibited aberrant patterns of expression in some glioblastoma multiforme samples compared to normal brain tissue. Degradation has yet to be observed in other tumor settings, including breast cancer-derived cell lines overexpressing members of the erbE family of receptor tyrosine kinases. These findings support both unique and shared roles for Abi-l and Abi-2 in mammalian development and suggest Abi degradation may be important in malignant transformation mediated by certain oncogenes.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADB259879
Entities
People
- Ann Marie Pendergast
- Kevin Courtney
Organizations
- Duke University Hospital