Work

Phosphorylation of the Tumor Suppressor Adenomatous Polyposis Coli (APC) by the Cyclin-dependent Kinase p34

Year: 1997

Type: article

Abstract: Mutations in the tumor suppressor gene APC invariably lead to the development of colorectal cancer. The vast majority of these mutations are nonsense or frameshifts resulting in nonfunctional, truncated APC protein products. Eleven cyclin-dependent kinase (CDK) consensus phosphorylation sites have been identified in the frequently deleted carboxyl-terminal region of APC; loss of these phosphorylation sites by mutation could therefore compromise the ability of APC to inhibit cell growth. This report demonstrates that immunoprecipitates of full-length, but not truncated, APC protein include a mitosis-specific kinase activity in vivo. Biochemical and Western analysis of these immunoprecipitates confirms the presence of the CDK p34(cdc2). We also show that APC is a substrate for recombinant human p34(cdc2)-cyclin B1. Modification of APC by p34(cdc2) implicates phosphorylation as a mechanism for regulating APC function via a link to the cell cycle.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.272.35.21681

Authors: Chris Trzepacz, Andrew M. Lowy, Jennifer J. Kordich, Joanna Groden

Institution: University of Cincinnati

Language: English

Topic: Cancer-related Molecular Pathways

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430