RNF114 suppresses metastasis through regulation of PARP10 in cervical cancer cells

Abstract

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ADP-Ribosylation as Post-Translational Modification of Proteins: Use of Inhibitors in Cancer Control

“…In the first years, the developed inhibitors were designed targeting a group of ART enzymes; in recent years, novel compounds have been developed specifically for a single ART enzyme, with effects in the nanomolar concentration. For instance, there are new inhibitors targeting just ARTD10 [ 126 , 130 , 131 , 132 , 133 ], ARTD11 [ 128 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 ], or ARTD14/PARP7 [ 145 , 146 , 147 ].…”

“…ARTD10 has tumor suppressor activity by inhibiting myc and by the MARylation of Aurora A kinase, inhibiting its phosphorylation on the same residue: The MARylation is exerted after interacting with the ubiquitin ligase RNF114, which ubiquitylates ARTD10, activating it; a loss of RNF114 in cancers (mutation, deletion, downregulation) may lead to a loss in ARTD10 activity [ 1 , 133 ]. ARTD10 may also have oncogenic activity, being involved in some cancers, promoting the proliferation and restart of stalled replication forks, and alleviating cell survival during replication stress [ 1 , 148 ].…”

Adp-Ribosylation as Post-Translational Modification of Proteins: Use of Inhibitors in Cancer Control

“…In the beginning years, the developed inhibitors were designed targeting a group of ART enzymes; in recent years, novel compounds have been developed specific for a single ART enzyme, with effects at nanomolar concentration. For instance, there are new inhibitors targeting just ARTD10 [120,[127][128][129][130], ARTD11 [122,[131][132][133][134][135][136][137][138][139][140][141][142][143][144]. or ARTD14/PARP7 [142][143][144].…”

“…ARTD10 has tumor suppressor activity by inhibiting myc, and by MARylation of Aurora A kinase, inhibiting its phosphorylation on the same residue: The MARylation is exerted after interaction with the ubiquitin ligase RNF114, that ubiquitylates ARTD10, activating it; a loss of RNF114 in cancers (mutation, deletion, downregulation) may lead to loss in ARTD10 activity [1,130]. ARTD10 may have also oncogenic activity, being involved in some cancers, promoting proliferation and restart of stalled replication forks, alleviating cell survival during replication stress [1,145].…”

“…MARylation of ARTD10 is recognized by ARTD8/PARP14, that is docked to the MAR structure to form a protein complex. Several molecules have shown the potential to selectively inhibit ARTD10 [127][128][129][130]14], such as the cell-permeable OU135, a 3,4-dihydroisoquinolin-1(2H)-one that contains a methyl group at the C-5 position and a substituted pyridine at the C-6 position [128], and 4-benzyloxybenzimide derivatives [127]. The targets of ARTD10 that could require a fine tuning of MARylation are glycogen synthase kinase GSK3β, NEMO/IKK-γ, a subunit of NF-kB transcription factor, histone H3 and the polo-like kinase PLK1 [1].…”