Identification of the main ubiquitination site in human erythroid α‐spectrin

Galluzzi, Luca; Paiardini, Mirko; Lecomte, Marie‐Christine; Magnani, Mauro

doi:10.1016/s0014-5793(00)02333-4

Cited by 16 publications

(21 citation statements)

References 30 publications

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“…Some structural preferences exist for ubiquitin ligation of the targeted proteins such as preferred choice of lysines in α-helices, and then for easily accessible lysines in the loop regions. Our findings add to the growing list that indicates a bias towards a consensus sequence motif for ubiquitination by a given E3 [19][20][21][22][23][24][25]. Moreover, it appears that the E3 targets an accessible surface residue providing the selection process with a conformational recognition mechanism.…”

Section: Receptor Ubiquitination Implicated In Regulation Of Trkb Dowsupporting

confidence: 52%

Identification of a consensus site for TRAF6/p62 polyubiquitination

Jadhav

Geetha

Jiang

et al. 2008

Biochemical and Biophysical Research Communications

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Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an ubiquitin ligase that regulates a diverse array of physiological processes via forming Lys-63 linked polyubiquitin chains. In this study, the lysine selection process for TRAF6/p62 ubiquitination was examined. The protein sequence of two characterized TRAF6/p62 substrates, NRIF and TrkA, revealed a conserved consensus pattern for the ubiquitination site of these two TRAF6 substrates. The consensus pattern established in the verified substrates was common to the other Trk receptor family members, TrkB and TrkC. Interestingly, Lysine 811 in TrkB was selected for ubiquination, and mutation of Lysine 811 diminished the formation of TRAF6/p62 complex that is necessary for effective ubiquination. Moreover, downstream signaling was affected upon binding of BDNF to the mutant TrkB receptor. These findings reveal a possible selection process for targeting a specific lysine residue by a single E3 ligase and underscore the role of the scaffold, p62, in this process. KeywordsUbiquitination; Ub ligase; TRAF6; p62; Trk Many adaptors have been identified in studies of other neuronal tyrosine kinases that may also prove to function in Trk receptor-mediated signaling [1]. Cytoplasmic protein p62 was identified as an interacting partner of atypical protein kinase C (PKC) [2] and has been shown to contain several protein-protein interacting modules that enable the protein to serve as a scaffold for activation of the transcription factor NF-κB [3]. The multidomain protein structure of p62 is suggestive of diverse protein-protein interactions and its link in cellular functions. The functional motifs in p62 include a Phox and Bem1p domain (PB1) domain that embeds an octicosapeptide Phox, Cdc and the atypical PKC-interaction domain (AID) (OPCA) motif, a ZZ zinc finger, a binding site for Tumor necrosis factor Receptor-Associated Factor 6 (TRAF6), two PEST sequences, and an Ubiquitin-associated (UBA) domain [4]. The Cterminal ubiquitin-associated domain (UBA) was discovered to bind non-covalently to ubiquitin [5]. In vitro binding studies have unveiled p62 as a unique ubiquitin-binding protein, which binds polyubiquitin non-covalently through its C-terminus [6].Ubiquitination of eukaryotic proteins regulates a broad range of cellular processes. E3 Ub ligases are known to interact with specific substrates either directly or through adaptor proteins. *Corresponding author. Fax: +1 (334) 844-5255, Email address: wootemw@auburn.edu (M. Wooten). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. . High substrate specificity of the ...

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Section: Receptor Ubiquitination Implicated In Regulation Of Trkb Dowsupporting

confidence: 52%

Identification of a consensus site for TRAF6/p62 polyubiquitination

Jadhav

Geetha

Jiang

et al. 2008

Biochemical and Biophysical Research Communications

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“…It is possible that the association of ␣-and ␤-Spectrin blocks ubiquitination of ␣-Spectrin and its subsequent degradation via the proteasome. Ubiquitination has been previously reported for ␣-Spectrin (Corsi et al, 1995;Galluzzi et al, 2001) and may thus help to define the correct protein-expression levels.…”

Section: Discussionmentioning

confidence: 80%

Distinct functions of α-Spectrin and β-Spectrin during axonal pathfinding

Hülsmeier¹,

Pielage²,

Rickert

et al. 2007

Development

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Cell-shape changes during development require a precise coupling of the cytoskeleton with proteins situated in the plasma membrane. Important elements controlling the shape of cells are the Spectrin proteins that are expressed as a subcortical cytoskeletal meshwork linking specific membrane receptors with F-actin fibers. Here, we demonstrate that Drosophila karussell mutations affect ␤-spectrin and lead to distinct axonal patterning defects in the embryonic CNS. karussell mutants display a slitsensitive axonal phenotype characterized by axonal looping in stage-13 embryos. Further analyses of individual, labeled neuroblast lineages revealed abnormally structured growth cones in these animals. Cell-type-specific rescue experiments demonstrate that ␤-Spectrin is required autonomously and non-autonomously in cortical neurons to allow normal axonal patterning. Within the cell, ␤-Spectrin is associated with ␣-Spectrin. We show that expression of the two genes is tightly regulated by post-translational mechanisms. Loss of ␤-Spectrin significantly reduces levels of neuronal ␣-Spectrin expression, whereas gain of ␤-Spectrin leads to an increase in ␣-Spectrin protein expression. Because the loss of ␣-spectrin does not result in an embryonic nervous system phenotype, ␤-Spectrin appears to act at least partially independent of ␣-Spectrin to control axonal patterning.

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“…The erythrocyte AE1 interacts with protein 4.1, ankyrin and spectrin, which comprise the erythrocyte cytoskeleton, and the importance of the interactions in the shape maintenance and deformability of erythrocytes is well-established (Walensky et al, 1998;Galluzzi et al, 2001;An et al, 2005). Recent studies have indicated that the cytoskeleton in nucleated cells provides mechanical support to the cell plasma membrane, and cytoskeletal networks are present in various intracellular structures that are involved in the regulation of major cellular functions, such as morphogenesis, cell proliferation, cell migration and cell-cell contact (Gascard and Mohandas, 2000;Takakuwa, 2000;Durham and Herman, 2009).…”

Section: Discussionmentioning

confidence: 99%

Induction of anion exchanger-1 translation and its opposite roles in the carcinogenesis of gastric cancer cells and differentiation of K562 cells

Zhang

et al. 2010

Oncogene

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Anion exchanger-1 (AE1), an erythroid-specific membrane protein, mediates the Cl À /HCO À 3 exchange across the plasma membrane and regulates intracellular pH. We have found that AE1 was unexpectedly expressed in gastric cancer cells and participated in the tumorigenesis of the cancer. Here, we focus on the induction of AE1 expression and its role in gastric carcinogenesis as well as in the differentiation of K562 cells. The results show that expression of AE1 is not related to genetic mutation or the mRNA level, but rather, that it is modulated by miR-24. miR-24 decreases the expression of AE1 through binding to the 3 0 UTR of AE1 mRNA. Transfection of an miR-24 into gastric cancer cells reduced the elevation of the AE1 protein, which resulted in return of AE1-sequestrated p16 to the nucleus, thereby inhibiting proliferation of the cells. Furthermore, the miR-24 inhibitor cooperated with hemin to induce the expression of AE1 in K562 cells and differentiation of the cells, which is consistent with results obtained from the cells cultured at pH 7.6 or from forced stable expression of AE1. These findings establish a novel regulation of miR-24-related AE1 expression in gastric carcinogenesis and erythropoiesis.

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Identification of the main ubiquitination site in human erythroid α‐spectrin

Cited by 16 publications

References 30 publications

Identification of a consensus site for TRAF6/p62 polyubiquitination

Identification of a consensus site for TRAF6/p62 polyubiquitination

Distinct functions of α-Spectrin and β-Spectrin during axonal pathfinding

Induction of anion exchanger-1 translation and its opposite roles in the carcinogenesis of gastric cancer cells and differentiation of K562 cells

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