Human DHHC proteins: A spotlight on the hidden player of palmitoylation

Korycka, Justyna; Lach, Agnieszka; Heger, Elżbieta; Bogusławska, Dżamila M.; Wolny, Marcin; Toporkiewicz, Monika; Augoff, Katarzyna; Korzeniewski, Jan; Sikorski, Aleksander F.

doi:10.1016/j.ejcb.2011.09.013

Cited by 128 publications

(114 citation statements)

References 98 publications

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“…The reaction is catalyzed by protein acyltransferases (PATs), while the removal of fatty acids from proteins is controlled by specific thioesterases. Twenty-three members of the PAT family containing a conserved Asp-His-His-Cys (DHHC) signature motif (1)(2)(3)(4)(5) and three thioesterases, APT1, APT2 (6), and APT1-like (7), have been identified to date. The reversibility of palmitoylation confers on this modification the property to regulate stability, intracellular trafficking, functional activity, and interactions of the proteins, as exemplified by the studies on the Ras family of small GTPases (8,9).…”

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confidence: 99%

ZDHHC3 Tyrosine Phosphorylation Regulates Neural Cell Adhesion Molecule Palmitoylation

Lievens

Kuznetsova

Kochlamazashvili

et al. 2016

Molecular and Cellular Biology

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The neural cell adhesion molecule (NCAM) mediates cell-cell and cell-matrix adhesion. It is broadly expressed in the nervous system and regulates neurite outgrowth, synaptogenesis, and synaptic plasticity. Previous in vitro studies revealed that palmitoylation of NCAM is required for fibroblast growth factor 2 (FGF2)-stimulated neurite outgrowth and identified the zinc finger DHHC (Asp-His-His-Cys)-containing proteins ZDHHC3 and ZDHHC7 as specific NCAM-palmitoylating enzymes. Here, we verified that FGF2 controlled NCAM palmitoylation in vivo and investigated molecular mechanisms regulating NCAM palmitoylation by ZDHHC3. Experiments with overexpression and pharmacological inhibition of FGF receptor (FGFR) and Src revealed that these kinases control tyrosine phosphorylation of ZDHHC3 and that ZDHHC3 is phosphorylated by endogenously expressed FGFR and Src proteins. By site-directed mutagenesis, we found that Tyr18 is an FGFR1-specific ZDHHC3 phosphorylation site, while Tyr295 and Tyr297 are specifically phosphorylated by Src kinase in cell-based and cell-free assays. Abrogation of tyrosine phosphorylation increased ZDHHC3 autopalmitoylation, enhanced interaction with NCAM, and upregulated NCAM palmitoylation. Expression of ZDHHC3 with tyrosine mutated in cultured hippocampal neurons promoted neurite outgrowth. Our findings for the first time highlight that FGFR-and Src-mediated tyrosine phosphorylation of ZDHHC3 modulates ZD-HHC3 enzymatic activity and plays a role in neuronal morphogenesis.

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confidence: 99%

ZDHHC3 Tyrosine Phosphorylation Regulates Neural Cell Adhesion Molecule Palmitoylation

Lievens

Kuznetsova

Kochlamazashvili

et al. 2016

Molecular and Cellular Biology

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“…The protein products of ZDHHC11 and ZDHHC11B are poorly characterized members of a palmitoyltransferase family 11 . Both protein-coding and non-coding ZDHHC11 transcripts are expressed in BL cell lines.…”

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confidence: 99%

ZDHHC11 and ZDHHC11B are critical novel components of the oncogenic MYC-miR-150-MYB network in Burkitt lymphoma

et al. 2017

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“…There are a total of 23 DHHC palmitoyltransferases in mammals (13). In the present study, we tested the hypothesis that one or more DHHC proteins among these 23 palmitoyltransferases may function as ClipR-59 palmitoyltransferase and have identified DHHC17 as the ClipR-59 palmitoyltransferase.…”

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confidence: 96%

DHHC17 Palmitoylates ClipR-59 and Modulates ClipR-59 Association with the Plasma Membrane

Ren

Sun

2013

Molecular and Cellular Biology

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b ClipR-59 interacts with Akt and regulates Akt compartmentalization and Glut4 membrane trafficking in a plasma membrane association-dependent manner. The association of ClipR-59 with plasma membrane is mediated by ClipR-59 palmitoylation at Cys534 and Cys535. To understand the regulation of ClipR-59 palmitoylation, we have examined all known mammalian DHHC palmitoyltransferases with respect to their ability to promote ClipR-59 palmitoylation. We found that, among 23 mammalian DHHC palmitoyltransferases, DHHC17 is the major ClipR-59 palmitoyltransferase, as evidenced by the fact that DHHC17 interacted with ClipR-59 and palmitoylated ClipR-59 at Cys534 and Cys535. By palmitoylating ClipR-59, DHHC17 directly regulates ClipR-59 plasma membrane association, as ectopic expression of DHHC17 increased whereas silencing of DHHC17 reduced the levels of ClipR-59 associated with plasma membrane. We have also examined the role of DHHC17 in Akt signaling and found that silencing of DHHC17 in 3T3-L1 adipocytes decreased the levels of Akt as well as ClipR-59 on the plasma membrane and impaired insulin-dependent Glut4 membrane translocation. We suggest that DHHC17 is a ClipR-59 palmitoyltransferase that modulates ClipR-59 plasma membrane binding, thereby regulating Akt signaling and Glut4 membrane translocation in adipocytes.

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Human DHHC proteins: A spotlight on the hidden player of palmitoylation

Cited by 128 publications

References 98 publications

ZDHHC3 Tyrosine Phosphorylation Regulates Neural Cell Adhesion Molecule Palmitoylation

ZDHHC3 Tyrosine Phosphorylation Regulates Neural Cell Adhesion Molecule Palmitoylation

ZDHHC11 and ZDHHC11B are critical novel components of the oncogenic MYC-miR-150-MYB network in Burkitt lymphoma

DHHC17 Palmitoylates ClipR-59 and Modulates ClipR-59 Association with the Plasma Membrane

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