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BMI-1

BMI1 is a stem cell gene as defined by the fact that its deficiency leads to compromised adult stem cell function. It was first identified in the early 1990s as a component of a key insertion/activation region of the Moloney murine leukemia virus. BMI1 encodes a 37 kDa polycomb group protein (PcG) from chromosome 10p11.23 in humans and 2 A3 in mice. The BMI1 protein contains a conserved RING finger domain in its N-terminal end and a central helix-turn-helix motif (H-T-H). BMI1 itself has no known enzymatic activity, but serves as the key regulatory component of the PRC1 complex (polycomb regulatory complex-1). 
This protein complex modulates chromatin structure and thereby regulates the transcription of a number of important genes, including the Ink4a locus which encodes two important tumor suppressor proteins p16Ink4a and p14Arf. There is increasing evidence that deregulated expression of PcG proteins contribute to cancer development. Aberrant overexpression of PcG proteins, in particular BMI1, is associated with a number of human malignancies. Importantly, BMI1 expression is thought to promote the stem state in tumor cells and overexpression of BMI1 correlates with therapy failure in many tumor types including those in breast, prostate, lung, and ovarian cancer patients. Additionally, experimental reduction of BMI1 protein levels results in apoptosis and/or senescence in tumor cells and increases susceptibility to cytotoxic agents and radiation therapy.

References

1.Cao L,et al. J Cell Biochem. 2011 Oct;112(10):2729-41.