The role of ErbB3 binding protein 1 in cancer: Friend or foe?

Nguyen, Dang Quan; Hoang, Don; Vo, Thanh Thao Nguyen; Huynh, Vu; Ghoda, Lucy; Marcucci, Guido; Nguyen, Le Xuan Truong

doi:10.1002/jcp.26951

Cited by 23 publications

(38 citation statements)

References 133 publications

(275 reference statements)

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“…The shorter p42 isoform lacks the N terminus of p48 and is considered to have a tumor suppressor role. Together with Rb, E2F1, and chromatin modifying proteins, HsEBP1 p42 represses cell proliferation (Liu et al, 2006;Ko et al, 2016;Nguyen et al, 2018;Nguyen et al, 2019). The internal methionine that initiates translation of the p42 isoform is not conserved in plants.…”

Section: Discussionmentioning

confidence: 99%

ErbB-3 BINDING PROTEIN 1 Regulates Translation and Counteracts RETINOBLASTOMA RELATED to Maintain the Root Meristem

et al. 2019

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The ErbB-3 BINDING PROTEIN 1 (EBP1) drives growth, but the mechanism of how it acts in plants is little understood. Here, we show that EBP1 expression and protein abundance in Arabidopsis (Arabidopsis thaliana) are predominantly confined to meristematic cells and are induced by sucrose and partially dependent on TARGET OF RAPAMYCIN (TOR) kinase activity. Consistent with being downstream of TOR, silencing of EBP1 restrains, while overexpression promotes, root growth, mostly under sucrose-limiting conditions. Inducible overexpression of RETINOBLASTOMA RELATED (RBR), a sugar-dependent transcriptional repressor of cell proliferation, depletes meristematic activity and causes precocious differentiation, which is attenuated by EBP1. To understand the molecular mechanism, we searched for EBP1-and RBR-interacting proteins by affinity purification and mass spectrometry. In line with the double-stranded RNA-binding activity of EBP1 in human (Homo sapiens) cells, the overwhelming majority of EBP1 interactors are part of ribonucleoprotein complexes regulating many aspects of protein synthesis, including ribosome biogenesis and mRNA translation. We confirmed that EBP1 associates with ribosomes and that EBP1 silencing hinders ribosomal RNA processing. We revealed that RBR also interacts with a set of EBP1-associated nucleolar proteins as well as factors that function in protein translation. This suggests EBP1 and RBR act antagonistically on common processes that determine the capacity for translation to tune meristematic activity in relation to available resources.

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Section: Discussionmentioning

confidence: 99%

ErbB-3 BINDING PROTEIN 1 Regulates Translation and Counteracts RETINOBLASTOMA RELATED to Maintain the Root Meristem

et al. 2019

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“…EBP1 is the human homologue of the yeast ribosome biogenesis factor Arx1 (Bradatsch et al, 2012;Kowalinski et al, 2007a) which also binds to the ribosomal exit site and is related to methionine aminopeptidases (MetAPs) (Kowalinski et al, 2007a;Kowalinski et al, 2007b). In addition, EBP1 has been described to be involved in cell proliferation (Squatrito et al, 2004) and human cancer (Nguyen et al, 2018).…”

Section: Ebp1 Binds To the Peptide Exit Site Of Hibernating Human Ribmentioning

confidence: 99%

Structure and function of yeast Lso2 and human CCDC124 bound to hibernating ribosomes

Wells

Buschauer

Mackens-Kiani

et al. 2020

Preprint

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150)Cells adjust to nutrient deprivation by reversible translational shut down. This is accompanied by maintaining inactive ribosomes in a hibernation state, where they are bound by proteins with inhibitory and protective functions. In eukaryotes, such a function was attributed to Stm1 (SERBP1 in mammals), and recently Lso2 (CCDC124 in mammals) was found to be involved in translational recovery after starvation from stationary phase. Here, we present cryo-electron microscopy (cryo-EM) structures of translationally inactive yeast and human ribosomes. We found Lso2/CCDC124 accumulating on idle ribosomes in the non-unrotated state, in contrast to Stm1/SERBP1-bound ribosomes, which display a rotated state. Lso2/CCDC124 bridges the decoding sites of the small with the GTPase-activating center of the large subunit. This position allows accommodation of the Dom34-dependent ribosome recycling system, which splits Lso2-containing but not Stm1-containing ribosomes. We propose a model in which Lso2 facilitates rapid translation reactivation by stabilizing the recycling-competent state of inactive ribosomes.

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“…It has attracted considerable attention due to its regulative role in cancer progression, although the question of being "friend or foe" 1 is still unanswered. This uncertainty is based on the contradictory functions of the two splice variants p42 and p48, with p42 (lacking 54 N-terminal residues) acting as tumor suppressor and p48 promoting cell proliferation 1 . First described as part of the ErbB3 receptor pathway 2 , it has been further on identified as an IRES-transacting factor (ITAF45) initiating viral mRNA translation 3 .…”

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confidence: 99%

MetAP-like Ebp1 occupies the human ribosomal tunnel exit and recruits flexible rRNA expansion segments

et al. 2020

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Human Ebp1 is a member of the proliferation-associated 2G4 (PA2G4) family and plays an important role in cancer regulation. Ebp1 shares the methionine aminopeptidase (MetAP) fold and binds to mature 80S ribosomes for translational control. Here, we present a cryo-EM single particle analysis reconstruction of Ebp1 bound to non-translating human 80S ribosomes at a resolution range from 3.3 to~8 Å. Ebp1 blocks the tunnel exit with major interactions to the general uL23/uL29 docking site for nascent chain-associated factors complemented by eukaryote-specific eL19 and rRNA helix H59. H59 is defined as dynamic adaptor undergoing significant remodeling upon Ebp1 binding. Ebp1 recruits rRNA expansion segment ES27L to the tunnel exit via specific interactions with rRNA consensus sequences. The Ebp1-ribosome complex serves as a template for MetAP binding and provides insights into the structural principles for spatial coordination of co-translational events and molecular triage at the ribosomal tunnel exit.

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The role of ErbB3 binding protein 1 in cancer: Friend or foe?

Cited by 23 publications

References 133 publications

ErbB-3 BINDING PROTEIN 1 Regulates Translation and Counteracts RETINOBLASTOMA RELATED to Maintain the Root Meristem

ErbB-3 BINDING PROTEIN 1 Regulates Translation and Counteracts RETINOBLASTOMA RELATED to Maintain the Root Meristem

Structure and function of yeast Lso2 and human CCDC124 bound to hibernating ribosomes

MetAP-like Ebp1 occupies the human ribosomal tunnel exit and recruits flexible rRNA expansion segments

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