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A cancer derived mutation in the Retinoblastoma gene with a distinct defect for LXCXE dependent interactions

Shauna A Henley13, Sarah M Francis13, Jordan Demone13, Peter Ainsworth4 and Frederick A Dick123*

Author Affiliations

1 London Regional Cancer Program, 790 Commissioners Road East, London, Ontario, N6A 4L6, Canada

2 Children's Health Research Institute, 800 Commissioners Road East, London, Ontario, N6A 4L6, Canada

3 Department of Biochemistry, University of Western Ontario, 1151 Richmond Street, London, Ontario, N6A 5B8, Canada

4 Molecular Diagnostics Laboratory, London Health Sciences Centre, 800 Commissioners Road East, London, Ontario, N6A 4L6, Canada

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Cancer Cell International 2010, 10:8  doi:10.1186/1475-2867-10-8

Published: 18 March 2010



The interaction between viral oncoproteins such as Simian virus 40 TAg, adenovirus E1A, and human papilloma virus E7, and the retinoblastoma protein (pRB) occurs through a well characterized peptide sequence, LXCXE, on the viral protein and a well conserved groove in the pocket domain of pRB. Cellular proteins, such as histone deacetylases, also use this mechanism to interact with the retinoblastoma protein to repress transcription at cell cycle regulated genes. For these reasons this region of the pRB pocket domain is thought to play a critical role in growth suppression.


In this study, we identify and characterize a tumor derived allele of the retinoblastoma gene (RB1) that possesses a discrete defect in its ability to interact with LXCXE motif containing proteins that compromises proliferative control. To assess the frequency of similar mutations in the RB1 gene in human cancer, we screened blood and tumor samples for similar alleles. We screened almost 700 samples and did not detect additional mutations, indicating that this class of mutation is rare.


Our work provides proof of principal that alleles encoding distinct, partial loss of function mutations in the retinoblastoma gene that specifically lose LXCXE dependent interactions, are found in human cancer.