ArticleInternational journal of biological sciences2007
MCEF is localized to the nucleus by protein sequences encoded within three distinct exons, where it represses HIV-1 Tat-transactivation of LTR-directed transcription.
Article in International journal of biological sciences, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- Modeling by disruption and a selected-for partner for the nude locus.EMBO reports · 2021Article
- Cat and Mouse: HIV Transcription in Latency, Immune Evasion and Cure/Remission Strategies.Viruses · 2019Review
- DOT1L safeguards cartilage homeostasis and protects against osteoarthritis.Nature communications · 2017Article
- Can the HIV-1 splicing machinery be targeted for drug discovery?HIV/AIDS (Auckland, N.Z.) · 2017Review
- Curb challenges of the "Trojan Horse" approach: smart strategies in achieving effective yet safe cell-penetrating peptide-based drug delivery.Advanced drug delivery reviews · 2013Review
- Regulation of AMP-activated protein kinase signaling by AFF4 protein, member of AF4 (ALL1-fused gene from chromosome 4) family of transcription factors, in hypothalamic neurons.The Journal of biological chemistry · 2012Article
- AF4 is a critical regulator of the IGF-1 signaling pathway during Purkinje cell development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
- The robotic mouse: understanding the role of AF4, a cofactor of transcriptional elongation and chromatin remodelling, in purkinje cell function.Cerebellum (London, England) · 2009Review
- In search of a function for the most frequent naturally-occurring length polymorphism (MFNLP) of the HIV-1 LTR: retaining functional coupling, of Nef and RBF-2, at RBEIII?International journal of biological sciences · 2007Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Translocations between the human Mixed Lineage Leukemia (MLL) and AF4 Family (AFF) member genes, are implicated in leukemia. Mutations to AFFs can disrupt lymphopoesis, CNS development and spermatogenesis. However, despite the growing list of pathologies linked to AFF members, their evolutionary relationship and the structure/function of individual members, remain to be elucidated. Here, we first report that database mining and phylogenetic analysis with AFF proteins from multiple species, revealed two monophyletic sister clades, suggesting a common Bilateria ancestor. We then examined the structure/function of the most recently discovered AFF member, MCEF (also known as AF5q31 or AFF4). In silico, the human MCEF gene was found to have 21 exons, and code for a protein with seven nuclear localization sequences (NLS). In HeLa cells, an MCEF-EGFP fusion protein, localized exclusively to the nucleus. Consequently, we made twenty constructs, expressing MCEF deletion mutants fused to EGFP and/or DsRed fluorescent proteins. Three distinct protein sequences, encoded by three separate MCEF exons, were found to mediate nuclear localization, only two of which were predicted in silico. Importantly, we also found that ectopic expression of MCEF, repressed HIV-1 LTR-directed RNA Polymerase II transcription, at the level of Tat-transactivation. We suggest that portions of MCEF could be exploited for chimeric transcription factor repression (CTFR) of HIV-1.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.