to the ubiquitination process. The binding of bmi-1 to Ring 1B would activate the E3 ubiquitin ligase activity greatly. It is indicated that both the RING domain and the extended N-terminal tail contribute to the interaction of bmi-1 and Ring 1B. Clinical significance Overexpression of Bmi1 seems to play an important role in several types of cancer, such as bladder, skin, prostate, breast, ovarian, colorectal as well as hematological malignancies. Its amplification and overexpression is especially pronounced in mantle cell lymphomas. Inhibiting BMI1 has been shown to inhibit the proliferation of glioblastoma multiforme, chemoresistant ovarian cancer, prostatic, pancreatic and skin cancers. Colorectal cancer stem cell self-renewal was reduced by BMI1 inhibition. The colon cancer stem cells in mouse xenografts could be eliminated by inhibiting BMI-1 gene, providing a novel potential method to treat colorectal cancer. According to a study by Canadian doctors, the loss of the BMI1 gene expression in human neurons may play a direct role in the development of Alzheimer's disease. Interactions BMI1 has been shown to interact with: PHC1, PHC2, RING1, and ZBTB16, References External links Further reading