Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human ELL gene, which is a frequent target for translocation in acute myeloid leukemia, was initially isolated from rat liver nuclei and found to be an RNA polymerase II elongation factor. Based on homology to ELL, we later cloned ELL2 and demonstrated that it can also increase the catalytic rate of transcription elongation by RNA polymerase II. To better understand the role of ELL proteins in the regulation of transcription by RNA polymerase II, we have initiated a search for proteins related to ELLs. In this report, we describe the molecular cloning, expression, and characterization of ELL3, a novel RNA polymerase II elongation factor approximately 50% similar to both ELL and ELL2. Our transcriptional studies have demonstrated that ELL3 can also increase the catalytic rate of transcription elongation by RNA polymerase II. The C-terminal domain of ELL, which we recently demonstrated to be required and sufficient for the immortalization of myeloid progenitor cells, shares strong similarities to the C-terminal domain of ELL3. ELL3 was localized by immunofluorescence to the nucleus of cells, and Northern analysis indicated that ELL3 is a testis-specific RNA polymerase II elongation factor.
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PMID:Identification, cloning, expression, and biochemical characterization of the testis-specific RNA polymerase II elongation factor ELL3. 1088 41

The ELL gene encodes an RNA polymerase II transcription factor that frequently undergoes translocation with the MLL gene in acute human myeloid leukemia. Here, we report that ELL can regulate cell proliferation and survival. In order to better understand the physiological role of the ELL protein, we have developed an ELL-inducible cell line. Cells expressing ELL were uniformly inhibited for growth by a loss of the G(1) population and an increase in the G(2)/M population. This decrease in cell growth is followed by the condensation of chromosomal DNA, activation of caspase 3, poly(ADP ribose) polymerase cleavage, and an increase in sub-G(1) population, which are all indicators of the process of programmed cell death. In support of the role of ELL in induction of cell death, expression of an ELL antisense RNA or addition of the caspase inhibitor ZVAD-fmk results in a reversal of ELL-mediated death. We have also demonstrated that the C-terminal domain of ELL, which is conserved among the ELL family of proteins that we have cloned (ELL, ELL2, and ELL3), is required for ELL's activity in the regulation of cell growth. These novel results indicate that ELL can regulate cell growth and survival and may explain how ELL translocations result in the development of human malignancies.
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PMID:Functional analysis of the leukemia protein ELL: evidence for a role in the regulation of cell growth and survival. 1123 4