Sunday 19 March 2006
PRDM2, originally isolated from its interaction with the RB tumor suppressor protein, was the first SET domain protein (SETs) demonstrated to be a tumor suppressor. The PRDM2 SET domain was recently shown to be a histone H3 Lys 9-specific methyltransferase.
The PRDM2 gene is situated on chromosome 1p36 in one of the most frequently deleted regions in human cancers, and PRDM2 has been found to be inactivated by mutations or DNA methylation in a wide variety of human tumors including breast cancer, liver cancer, colorectal cancer, lung cancer, lymphomas, and melanomas.
The RIZs gene produces two proteins, PRDM2 (RIZ1) and RIZ2, because of the use of alternative promoters. Interestingly, only PRDM2 harbors a SET domain and appears to be the main target of inactivation in tumors, and mice lacking Riz1 function only are prone to tumor formation.
In accordance with a tumor-suppressive function of PRDM2, ectopic expression in cancer cell lines results in cell cycle arrest and/or apoptosis.
Tam W, Gomez MF, Chadburn A, Knowles DM, Houldsworth J. Lack of A563G (I188V) missense mutation in RIZ/ PRDM2 in human diffuse large B-cell lymphomas. Genes Chromosomes Cancer. 2007 Apr;46(4):416-8.