Abstract
PARP12 is a mono-ADP-ribosyltransferase, but its function remains largely unknown. Here, we identified four-and-a-half LIM-only protein 2 (FHL2) as a functional partner of PARP12 through protein affinity purification. Although PARP12 did not mono-ADP-ribosylate FHL2 in vitro and in vivo, PARP12 deficiency decreased the protein level of FHL2 by promoting its ubiquitination and increased the expression level of transforming growth factor beta1 (TGF-β1), which is independent of PARP12 enzymatic activity. We also provided evidence that PARP12 deficiency increased the migration and invasion of hepatocellular carcinoma (HCC) cells and promoted HCC metastasis in vivo by regulating the epithelial–mesenchymal transition process. These results indicated that PARP12 is a tumor suppressor that plays an important role in HCC metastasis through the regulation of FHL2 stability and TGF-β1 expression.
Highlights
ADP-ribosylation is an evolutionarily conserved posttranslational modification that plays important roles in expanding the range of cellular functions, such as DNA repair and replication, chromatin remodeling, transcription, and telomere homeostasis[1,2]
Mass spectrometry analysis revealed that four-and-ahalf LIM-only protein 2 (FHL2), a LIM-only protein that belongs to the four-and-a-half LIM-only protein family, was present in the Poly(ADP-ribose) polymerase 12 (PARP12) affinity purification complex (Fig. 1a)
These results indicated that FHL2 was a partner of PARP12
Summary
ADP-ribosylation is an evolutionarily conserved posttranslational modification that plays important roles in expanding the range of cellular functions, such as DNA repair and replication, chromatin remodeling, transcription, and telomere homeostasis[1,2]. ADP-ribosylation is mainly catalyzed by intracellular ADP-ribosyltransferases (ARTs), which use nicotinamide adenine dinucleotide (NAD+) to transfer ADP-ribose moieties to specific residues on target proteins, leading to mono-ADPribosylation (MARylation) or the formation of linear or branched chains of poly-ADP-ribose (PARylation)[1,2]. Poly(ADP-ribose) polymerase 12 (PARP12), known as ARTD12, is a mono-ADP-ribosyltransferase. It was originally identified as a putative antiviral gene belonging to a large family of interferon-stimulated genes whose expression is often induced during viral infections[9,10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
