Chromosomal DNA and p53 stability, ubiquitin system and apoptosis in B-CLL lymphocytes

Leukemia & Lymphoma
R BlaiseJ Delic

Abstract

The ubiquitin system regulates diverse biological processes such as DNA replication and repair, biogenesis of ribosome, peroxisome and nucleosome, cell cycle, stress response and signal transduction pathways. Thus, the reported role of the ubiquitin system in apoptotic death control as well the alteration of its control in carcinogenesis should come as no surprise. Indeed, we and other groups have reported that the ubiquitin system is involved in apoptotic cell death of normal human lymphocytes and that this control is altered in B lymphocytes derived from chronic lymphocytic leukemia patients (B-CLL), rendering these malignant cells hypersensitive to specific inhibition of protein degradation/processing through proteasomal function. This approach recently allowed us to demonstrate that the stability of the tumor suppressor and pro-apoptotic protein p53 is differentially regulated in B-CLL versus normal lymphocytes and that this difference might at least partly explain the impaired response of B-CLL lymphocytes to apoptotic death activation. These results strongly suggest an imbalance in p53 regulation in B-CLL cells that leads to a variable response to DNA damage and constitutively expressed chromosomal instability. The questi...Continue Reading

Citations

Dec 4, 2003·Journal of Virology·Christophe DebacqLuc Willems
Feb 18, 2016·Journal of Cancer Research and Therapeutics·Fengyan LiMeiyan Wei
Apr 24, 2007·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Claudia KallaPeter Lichter
Sep 12, 2006·Progress in Retinal and Eye Research·Luo Lu
Mar 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lance F BartonJohn J Monaco

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