Primary research

Ku86 exists as both a full-length and a protease-sensitive natural variant in multiple myeloma cells

Charles A Gullo^1,2 , Feng Ge² , Geraline Cow^1,2 and Gerrard Teoh^2,3

¹Department of Clinical Research (DCR), Cancer Immunology Laboratory, Singapore General Hospital (SGH), Outram Road, Singapore 169608, Singapore

²Multiple Myeloma Research Laboratory (MMRL), Singapore Health Services Pte Ltd (SingHealth), 7 Hospital Drive, Block A #02-05, Singapore 169611, Singapore

³Department of Hematology, SGH, Outram Road, Singapore 169608, Singapore

author email corresponding author email

Cancer Cell International 2008, 8:4doi:10.1186/1475-2867-8-4

Published:	29 April 2008

Abstract

Background

Truncated variants of Ku86 protein have previously been detected in 86% to 100% of freshly isolated patient multiple myeloma (MM) cells. Since, the Ku70/Ku86 heterodimer functions as the regulatory subunit of the DNA repair enzyme, DNA-dependent protein kinase, we have been interested in the altered expression and function of Ku86 variant (Ku86v) proteins in genome maintenance of MM.

Results

Although, a number of studies have suggested that truncated forms of Ku proteins could be artificially generated by proteolytic degradation in vitro in human lymphocytes, we now show using whole cell immunoblotting that the RPMI-8226 and SGH-MM5 human MM cell lines consistently express full-length Ku86 as well as a 69-kDa Ku86v; a C-terminus truncated 69-kDa variant Ku86 protein. In contrast, Ku86v proteins were not detected in the freshly isolated lymphocytes as was previously reported. Data also indicates that the Ku86v was not generated as a result of carbohydrate modification but that serine proteases may act on the full-length form of the protein.

Conclusion

These data confirm that MM cells contain bona fide Ku86v proteins that were generated intracellularly by a post-transcriptional mechanism, which required proteolytic processing.