Transcription elongation is an important regulatory step in development, differentiation, and cancer. The ELL (eleven-nineteen lysine-rich leukemia) proteins are encoded by three closely related genes (ELL1, 2 and 3) essential in controlling transcription elongation as part of the super elongation complexes (SEC) for mRNAs or the little elongation complexes (LEC) for snRNAs. A conserved portion of the ELL2 protein interacts with the central portion of the AFF4 scaffold protein (at its elbow region) to stabilize the SEC in HIV infections. In antibody secreting cells, ELL2 has an important role in production of the secretory-specific Ig heavy chain, the unfolded protein response, and glycosylation. At least 25 tumor tissue types have mutations in ELL2. Having too much or too little ELL can cause cancer; this dichotomy may potentially be explained by cells expressing varying levels of the transcriptional targets of the SEC or the levels of a number of ELL-interacting protein factors in those tumors such as EAF2, EAP30/ SNF8, HIF-1 alpha, RB, SIAH1, or c-MYC which can be ubiquitinylated by ELL1. Recent studies have linked expression mutations in ELL2 with a non-secreting form of familial multiple myeloma. We conclude that ELL2 can serve not just as a factor to enhance Ig heavy chain mRNA processing but also as an important target for some forms of cancer and for growth regulation of lymphocytes.
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