Disease relevance of ELL

• The human ELL gene on chromosome 19p13.1 undergoes frequent translocations with the trithorax-like MLL gene on chromosome 11q23 in acute myeloid leukemia [1].
• MLL is fused to ENL or ELL in acute leukemias that contain t(ll;19)(q23;p13) [2].
• CONCLUSIONS: Men with the p53 codon 72 Pro/Pro genotype appear to be at reduced risk of prostate cancer [3].
• BACKGROUND: Men and women with hypertension are at increased risk for cardiovascular disease, especially when left ventricular hypertrophy is present [4].
• BACKGROUND: Men with benign prostatic hyperplasia can be treated with alpha 1-adrenergic-antagonist drugs that relax prostatic smooth muscle or with drugs that inhibit 5 alpha-reductase and therefore reduce tissue androgen concentrations [5].

Psychiatry related information on ELL

• BACKGROUND: Men with deviant sexual behavior, or paraphilia, are usually treated with psychotherapy, antidepressant drugs, progestins, and antiandrogens, but these treatments are often ineffective [6].
• Simultaneous stimulation of slow-wave sleep and growth hormone secretion by gamma-hydroxybutyrate in normal young Men [7].
• TARGET POPULATION: Men 60 years of age with erectile dysfunction [8].
• PARTICIPANTS: Men and women (n = 2500) who were between 35 and 54 years old at baseline, followed for 20 years in Framingham, Massachusetts. MEASUREMENTS: Height, weight, lipid levels, blood pressure, smoking status, diet, physical activity, prevalent and incident cardiovascular disease, diabetes, other diseases, and mortality rate were assessed [9].
• RESULTS: Men living in stepfamilies had-significantly higher levels of depressive symptoms before and after the birth than did men in more traditional families [10].

High impact information on ELL

• BACKGROUND: Men with isolated gonadotropin-releasing hormone (GnRH) deficiency typically present with an absence of pubertal development [11].
• The human ELL gene on chromosome 19 undergoes frequent translocations with the trithorax-like MLL gene on chromosome 11 in acute myeloid leukemias [12].
• Functionally, ELL resembles Elongin (SIII), a transcription elongation factor regulated by the product of the von Hippel-Lindau (VHL) tumor suppressor gene [12].
• An RNA polymerase II elongation factor encoded by the human ELL gene [12].
• RESULTS: Men exposed prenatally to severe maternal nutritional deficiency during the first and/or second trimesters of pregnancy exhibited increased risk for ASPD (adjusted odds ratio [OR], 2.5; 95% confidence interval [CI], 1.5-4.2) [13].

Chemical compound and disease context of ELL

• SETTING: Multicenter, collaborative, primary prevention trial conducted at 22 clinical centers in the United States. PARTICIPANTS: Men (n = 10,529) who were 35 to 57 years old at baseline and who were in the upper 10% to 15% of risk for coronary heart disease because of smoking, high blood pressure, and elevated cholesterol level [14].
• CONCLUSION: Men with either serum testosterone or IGF-1 levels in upper quartile of the population distribution have an approximately two-fold higher risk for developing prostate cancer [15].
• PATIENTS AND METHODS: Men with metastatic prostate cancer (n = 161) were randomized to receive either daily prednisone alone or mitoxantrone (every 3 weeks) plus prednisone [16].
• MATERIALS AND METHODS: Men with HRPC, bone metastases, and bone pain were randomly assigned to receive clodronate 1,500 mg administered intravenously (IV) or placebo every 3 weeks, in combination with mitoxantrone 12 mg/m2 IV every 3 weeks and prednisone 5 mg orally bid [17].
• METHODS: Men and women older than 45 years were recruited from 3 hospitals in south central Connecticut. Eligibility criteria included a recent TIA or nondisabling ischemic stroke, no history of physician-diagnosed diabetes mellitus, and a fasting plasma glucose level less than 126 mg/dL (<7.0 mmol / L) [18].

Biological context of ELL

• ELL binding regulates U19/Eaf2 intracellular localization, stability, and transactivation [19].
• Functional analysis of the leukemia protein ELL: evidence for a role in the regulation of cell growth and survival [20].
• 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 [20].
• Here, we report that ELL can regulate cell proliferation and survival [20].
• Transient transfections demonstrated that ELL increased receptor transcriptional potency and hormonal efficacy, indicating that ELL behaves as a bona fide MR coactivator [21].

Anatomical context of ELL

• Using specific antibodies, the endogenous EAF1 and ELL proteins were coimmunoprecipitated from multiple cell lines [22].
• We reconstituted lethally irradiated congenic mice with bone marrow progenitors transduced with MLL-ELL or the control MIE vector encoding the enhanced green fluorescent protein [23].
• 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 [24].
• RESULTS: Men represented 53.8% of the cohort, and the parotid gland and palate were affected by MEC in 35.2% and 23.7%, respectively [25].
• (c) Men and women with a male abdominal type of obesity are more susceptible to the effect of excess body fat on lipid and carbohydrate metabolism [26].

Associations of ELL with chemical compounds

• A highly basic, lysine-rich motif of the predicted ELL protein is homologous to similar regions of several proteins, including the DNA-binding domain of poly(ADP-ribose) polymerase [27].
• Of major interest, ELL differentially modulates steroid receptor responses, with striking opposite effects on hMR and glucocorticoid receptor-mediated transactivation, without affecting that of androgen and progesterone receptors [21].
• These findings allow us to propose the concept of "transcriptional selector" for ELL on steroid receptor transcriptional functions [21].
• RESULTS: Men with diabetes had significantly lower plasma levels of free (4.96 nmol/L compared with 5.58 nmol/L) and total testosterone (14.7 nmol/L compared with 17.4 nmol/L), dihydrotestosterone (428 pg/mL compared with 533 pg/mL), and dehydroepiandrosterone sulfate (DHEA-S) (1.92 mumol/L compared with 2.42 mumol/L) than nondiabetic men [28].
• SETTING: Community. PARTICIPANTS: Men 53 to 88 years of age from the Rancho Bernardo, California, cohort who were screened for diabetes using an oral glucose tolerance test [28].

Physical interactions of ELL

• We identified a protein-protein interaction domain within the amino-terminus of ELL that binds to both EAF1 and EAF2 [29].
• Here we report that the EAP30 subunit of the ELL complex has sequence homology to the Saccharomyces cerevisiae SNF8, whose genetic analysis suggests its involvement in the derepression of gene expression [30].
• The Holo-ELL complex can increase the catalytic rate of transcription elongation by RNA polymerase II [31].

Regulatory relationships of ELL

• Through this interaction, ELL inhibits both sequence-specific transactivation and sequence-independent transrepression by p53 [32].
• However, unlike the ELL polypeptide alone, the Holo-ELL complex is not capable of negatively regulating polymerase activity in promoter-specific transcription in vitro [31].

Other interactions of ELL

• Confocal microscopy revealed that endogenous EAF2 and ELL colocalized in a nuclear speckled pattern [29].
• By confocal microscopy, endogenous EAF1 and ELL colocalized in a distinct nuclear speckled pattern [22].
• This amino-terminal interaction domain is disrupted in the formation of the MLL-ELL fusion protein [29].
• In this report, we identify and characterize two overlapping ELL functional domains that govern its interaction with RNA polymerase II and the ternary elongation complex [1].
• Thus, ELL acts as a negative regulator of p53 in transcription [32].

Analytical, diagnostic and therapeutic context of ELL

• METHODS: Using co-transfection, co-immunoprecipitation, protein stability assay and transactivation assay, we characterized the consequence of ELL binding to U19/Eaf2 [19].
• To determine the subcellular localization of ELL, we developed a polyclonal antiserum to ELL that was used for immunofluorescence studies in COS-7, HeLa, NIH 3T3, and A7r5 cells [33].
• In this report we describe molecular cloning, expression, and characterization of human ELL2, a novel RNA polymerase II elongation factor 49% identical and 66% similar to ELL [34].
• We therefore used reverse transcriptase-polymerase chain reaction (RT-PCR) assays to analyze 26 cases of childhood acute leukemia containing t(11;19) to determine the frequencies of ENL and ELL involvement [2].
• CONCLUSIONS: This randomized study demonstrates that (1) ELL is frequently detected after treatment of in-stent restenosis with balloon angioplasty, that (2) ELL influences the long-term clinical outcome of these patients, and that (3) repeat stent implantation prevents ELL [35].

References