BPOZ-2 directly binds to eEF1A1 to promote eEF1A1 ubiquitylation and degradation and prevent translation.

Genes Cells

Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba, Japan.

Published: June 2008

Bood POZ containing gene type 2 (BPOZ-2), which contains ankyrin repeats, NLS, BTB/POZ domains and LXXLL motifs, is an adaptor protein for the E3 ubiquitin ligase scaffold protein CUL3. We isolated a cDNA encoding eukaryotic elongation factor 1A1 (eEF1A1) as a BPOZ-2 binding protein by screening a human thymus cDNA library using a yeast two-hybrid system. eEF1A1 is essential for translation and is also involved in the 26S proteasome-dependent degradation of misfolded or unfolded proteins. The binding between BPOZ-2 and eEF1A1 was confirmed by pull-down and immunoprecipitation assays in vitro and in vivo, respectively. BPOZ-2 binds to eEF1A1 through the ankyrin repeats and both BTB/POZ domains in BPOZ-2 and Domains I and III in eEF1A1. BPOZ-2 and eEF1A1 over-expressed in HEK 293T cells co-localized as speckles within the cytoplasm. BPOZ-2 promoted eEF1A1 ubiquitylation and degradation, suggesting that eEF1A1 is a substrate of BPOZ-2. BPOZ-2 inhibited GTP binding to eEF1A1 and prevented translation in in vitro translation assay using rabbit reticulocytes.

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1365-2443.2008.01191.xDOI Listing

Publication Analysis

Top Keywords

eef1a1
11
bpoz-2
10
binds eef1a1
8
eef1a1 ubiquitylation
8
ubiquitylation degradation
8
ankyrin repeats
8
btb/poz domains
8
eef1a1 bpoz-2
8
bpoz-2 eef1a1
8
bpoz-2 directly
4

Similar Publications

Small Molecule with Big Impact: Metarrestin Targets the Perinucleolar Compartment in Cancer Metastasis.

Cells

December 2024

Division of Cancer Immunology and Microbiology, Medicine, and Oncology Integrated Service Unit, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA.

Metarrestin (ML246) is a first-in-class pyrrole-pyrimidine-derived small molecule that selectively targets the perinucleolar compartment (PNC). PNC is a distinct subnuclear structure predominantly found in solid tumor cells. The occurrence of PNC demonstrates a positive correlation with malignancy, serving as an indicator of tumor aggressiveness, progression, and metastasis.

View Article and Find Full Text PDF

Deep multi-omics integration approach reveals new molecular features of uterine leiomyosarcoma.

Biochim Biophys Acta Mol Basis Dis

December 2024

Universidade Federal do Rio Grande do Norte, IMD, Ppg-Bioinformatica, Natal, Brazil; University of Southern California, Keck School of Medicine, Department of Translational Genomics, 1450 Biggy St., Los Angeles, CA 90089, United States of America. Electronic address:

Uterine leiomyosarcoma (uLMS) is a rare and aggressive cancer representing approximately 25 % of all uterine malignancies. The molecular heterogeneity and pathogenesis of uLMS are not well understood, and translational studies aimed at discovering the vulnerabilities of this tumor type are of high priority. We conducted an innovative comprehensive multi-omics integration study from DNA to protein using freshly frozen tumors.

View Article and Find Full Text PDF

Climate change and growing population and their strain on animal production are the impending challenges that the developing countries, like India, need to tackle in the coming days. This study aimed to detect and analyze the uncharacterized variation in the gene expression patterns with the change of condition, from thermoneutral to chronic hot-humid, in the Sahiwal cattle, one of the best breeds of milk-producing cattle in India, known for being heat-tolerant. Using RNA-Seq analysis on peripheral blood mononuclear cells (PBMCs), 4021 differentially expressed mRNAs (2772 upregulated, 1249 downregulated) and 1303 differentially expressed long non-coding RNAs (769 upregulated, 534 downregulated) were identified, with the thresholds of false discovery rate < 0.

View Article and Find Full Text PDF

Temporal alterations of the nascent proteome in response to mitochondrial stress.

Cell Rep

October 2024

Remedy International Research Agenda Unit, IMol Polish Academy of Sciences, 02-247 Warsaw, Poland; IMol Polish Academy of Sciences, 02-247 Warsaw, Poland. Electronic address:

Under stress, protein synthesis is attenuated to preserve energy and mitigate challenges to protein homeostasis. Here, we describe, with high temporal resolution, the dynamic landscape of changes in the abundance of proteins synthesized upon stress from transient mitochondrial inner membrane depolarization. This nascent proteome was altered when global translation was attenuated by stress and began to normalize as translation was recovering.

View Article and Find Full Text PDF

Selective translation of nuclear mitochondrial respiratory proteins reprograms succinate metabolism in AML development and chemoresistance.

Cell Stem Cell

December 2024

Department of Hematology, Zhongnan Hospital, Medical Research Institute, Wuhan University, Wuhan, China; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China; RNA Institute, Wuhan University, Wuhan, China. Electronic address:

Article Synopsis
  • Mitochondrial adaptations play a significant role in altering cellular energy and metabolism in human cancers, including acute myeloid leukemia (AML), but their precise regulation is not well understood.
  • Researchers identified the RAS effector RREB1 as an important regulator of mitochondrial protein translation, which impacts mitochondrial activity and metabolism in leukemia stem cells (LSCs).
  • Deleting RREB1 harms LSC function, but restoring a specific mitochondrial complex subunit can address these issues and make AML cells more responsive to treatment with venetoclax.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!