Structure function characterization of the ELL Associated Factor (EAF) from Schizosaccharomyces pombe

Dabas, Preeti; Sweta, Kumari; Ekka, Mary Krishna; Sharma, Nimisha

doi:10.1016/j.gene.2017.10.031

Cited by 5 publications

(10 citation statements)

References 45 publications

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“…We next wanted to determine whether AtEAF‐1 and AtEAF‐2 are functional orthologs of the S. pombe EAF protein? We have previously demonstrated that S. pombe cells lacking eaf + exhibit slower growth, as well as display growth‐related sensitivity towards DNA damaging agents 27 . Interestingly, we have also observed that the human EAF2 ortholog can partially rescue these phenotypes associated with absence of eaf + in S. pombe (unpublished data).…”

Section: Resultsmentioning

confidence: 69%

“…Our earlier work had shown that the carboxyl‐terminus of S. pombe EAF is intrinsically disordered 27 . Therefore, we next decided to employ computational disorder prediction tools to examine the presence of ordered and disordered regions within full‐length S. pombe and A. thaliana EAF orthologs.…”

Section: Resultsmentioning

confidence: 99%

“…Schizosaccharomyces pombe strains, FY254 ( h ‐ can1‐1 leu1‐32 ade6‐M210 ura4‐D18 ) (kind gift Prof. Susan Forsburg) and FY254Δ eaf , 27 were grown in EMM2 medium with the required supplements depending on the plasmid construct.…”

Section: Methodsmentioning

confidence: 99%

“…A single EAF homolog has been identified in S. pombe , and in contrast to its homologs in higher eukaryotes, its absence does not affect the viability of S. pombe 12 . However, depletion of EAF in S. pombe results in slow growth under optimum growth conditions, cell separation defect and genotoxic stress induced growth sensitivity 17,27 …”

Section: Introductionmentioning

confidence: 99%

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Arabidopsis thaliana possesses two novel ELL associated factor homologs

et al. 2021

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Transcription elongation is one of the key steps at which RNA polymerase II‐directed expression of protein‐coding genes is regulated in eukaryotic cells. Different proteins have been shown to control this process, including the ELL/EAF family. ELL Associated Factors (EAFs) were first discovered in a yeast two‐hybrid screen as interaction partners of the human ELL (Eleven nineteen Lysine‐rich Leukemia) transcription elongation factor. Subsequently, they have been identified in different organisms, including Schizosaccharomyces pombe. However, no homolog(s) of EAF has as yet been characterized from plants. In the present work, we identified EAF orthologous sequences in different plants and have characterized two novel Arabidopsis thaliana EAF homologs, AtEAF‐1 (At1g71080) and AtEAF‐2 (At5g38050). Sequence analysis showed that both AtEAF‐1 and AtEAF‐2 exhibit similarity with its S. pombe EAF counterpart. Moreover, both Arabidopsis thaliana and S. pombe EAF orthologs share conserved sequence characteristic features. Computational tools also predicted a high degree of disorder in regions towards the carboxyl terminus of these EAF proteins. We demonstrate that AtEAF‐2, but not AtEAF‐1 functionally complements growth deficiencies of Schizosaccharomyces pombe eaf mutant. We also show that only AtEAF‐1 displays transactivation potential resembling the S. pombe EAF ortholog. Subsequent expression analysis in A. thaliana showed that both homologs were expressed at varying levels during different developmental stages and in different tissues tested in the study. Individual null‐mutants of either AtEAF‐1 or AtEAF‐2 are developmentally normal implying their functional redundancy. Taken together, our results provide first evidence that A. thaliana also possesses functional EAF proteins, suggesting an evolutionary conservation of these proteins across organisms.

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Section: Resultsmentioning

confidence: 69%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Arabidopsis thaliana possesses two novel ELL associated factor homologs

et al. 2021

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“…In lower organisms, the EAF ortholog has been shown to play an important role in growth, DNA damage response, fertility, survival and development. EAF in S. pombe was shown to increase transcriptional elongation of spELL [4]; and deletion of spEAF inhibited growth and sensitized cells to DNA damage [5]. Deletion of eaf-1 in C. elegans resulted in decreased fertility, decreased survival and altered cuticle collagen function [6].…”

Section: Introductionmentioning

confidence: 99%

Conditional Deletion of Eaf1 Induces Murine Prostatic Intraepithelial Neoplasia in Mice

Pascal

Wang

et al. 2019

Neoplasia

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ELL-associated factor 1 is a transcription elongation factor that shares significant homology and functional similarity to the androgen-responsive prostate tumor suppressor ELL-associated factor 2. EAF2 is frequently down-regulated in advanced prostate cancer and Eaf2 deletion in the mouse induced the development of murine prostatic intraepithelial neoplasia. Here we show that similar to EAF2, EAF1 is frequently down-regulated in advanced prostate cancer. Co-downregulation of EAF1 and EAF2 occurred in 40% of clinical specimens with Gleason score >7. We developed and characterized a murine model of prostate-epithelial specific deletion of Eaf1 in the prostate and crossed it with our previously generated mouse with conventional deletion of Eaf2 . The prostates of Eaf1 deletion mice displayed murine prostatic intraepithelial neoplasia lesions with increased proliferation and inflammation. Combined deletion of Eaf1 and Eaf2 in the murine model induced an increased incidence in mPIN lesions characterized by increased proliferation and CD3+ T cells and CD19+ B cells infiltration compared to individual deletion of either Eaf1 or Eaf2 in the murine prostate. These results suggest that EAF1 may play a tumor suppressive role in the prostate. Cooperation between EAF1 and EAF2 may be important for prostate maintaining prostate epithelial homeostasis, and concurrent loss of these two tumor suppressors may promote prostate tumorigenesis and progression.

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