Ask about this productRelated genes to: RNF146 Blocking Peptide
- Gene:
- RNF146 NIH gene
- Name:
- ring finger protein 146
- Previous symbol:
- -
- Synonyms:
- DKFZp434O1427, dactylidin, dJ351K20.1
- Chromosome:
- 6q22.33
- Locus Type:
- gene with protein product
- Date approved:
- 2003-11-26
- Date modifiied:
- 2016-10-05
Related products to: RNF146 Blocking Peptide
Related articles to: RNF146 Blocking Peptide
- Poly(ADP-ribose) (PAR) is a polymer of ADP-ribose synthesized by four members of the ADP-ribose polymerase family of enzymes-PARP1, PARP2, PARP5a, and PARP5b. However, only PARP1 and PARP2 synthesize PAR in response to DNA breaks. PAR is defined as a protein post-translational modification, but it is also shown to exist as a DNA or RNA modification. Levels of PAR are further regulated by PARG, a PAR glycohydrolase that, together with PARP1 and PARP2, modulates the cellular level of DNA damage-induced PAR. The dynamic synthesis and degradation of PAR is critical to its regulatory role in DNA repair, and the DNA damage response, which in turn affects chromatin reorganization, replication, transcription, and cell death. PARP1/PARP2 activation and the accumulation of PAR can be considered sites of ongoing base excision repair or DNA single-strand break repair; however, numerous PARP1/PARP2 activators are also associated with replication stress and other DNA metabolic processes. Once formed, PAR chains facilitate the recruitment of DNA repair and DNA damage response (DDR) factors to sites of DNA damage or genomic insult via their PAR-binding domains (PBDs). Ten different PBDs recognize various regions of the PAR molecule, including the PAR binding motif, PAR binding Zinc finger, the WWE domain, and the macrodomain, among other PBDs. To facilitate cellular analysis of PAR dynamics, we used PBDs fused to enhanced green fluorescent protein (EGFP) to optimize cell-based quantitation of PAR foci. We describe an assay that uses a fragment of RNF146 encoding the PBD/WWE domain, linked to EGFP, to visualize and quantify PAR accumulation at sites of genomic insult and ongoing BER or SSBR. We describe experimental steps, including the production of lentiviral particles, transduction of the target cell line, treatment of mammalian cells to induce genomic DNA damage, acquisition of confocal fluorescence micrographs, and semi-automated quantification of the data. - Source: PubMed
Publication date: 2026/04/17
Roos Wynand PAl-Rahahleh Rasha QKoczor Christopher ABeers Libby ABoyang LouisSobol Robert W - Angiomotin-like 1 (AMOTL1), by regulating cell-cell junctions, cell polarity, and cell migration, plays a critical role in organogenesis and development. Recently, multiple studies have identified two hotspot mutations in AMOTL1, Arg157 (R157) and Pro160 (P160), in more than ten distinct families presenting with a spectrum of congenital defects, including facial dysmorphisms and cardiac abnormalities. However, the underlying pathogenic mechanism remains elusive. R157 and P160 are located in the highly conserved Tankyrase-binding motif (TBM) of AMOTL1. Here, we show that both the R157C and P160L mutants fail to interact with Tankyrase 1/2 and Ring finger protein 146, rendering them unable to undergo poly ADP-ribosylation, ubiquitination, and subsequent proteasomal degradation. As a result, these mutants are significantly stabilized and accumulate in the cytoplasm. Accumulated AMOTL1 mutants, in turn, disrupt cell junctions and focal adhesions, thereby inhibiting both the velocity and persistence of cell migration. Furthermore, during zebrafish embryonic development, expression of the R157C mutant leads to craniofacial malformations and defects in cardiac function and skeletal muscle. Our study confirms the role of AMOTL1 mutations in tissue development and uncovers the pathogenic mechanism at both molecular and cellular levels. - Source: PubMed
Luo JiaqianJin RuxinGeng FangWang YunyingZhu YuwenGao WenqiangGao WeiLi JianJiu YamingZhang RuilinYu Fa-XingWang Yu - To investigate RNF146 expression in triple-negative breast cancer (TNBC) and its role in modulating sensitivity to the PARP inhibitor olaparib, we analyzed RNF146 expression and its association with patient survival using The Cancer Genome Atlas (TCGA) database. Functional studies were performed in 4T1 cells with stable RNF146 overexpression generated via lentiviral transduction. Cell viability and clonogenic capacity were assessed by CCK-8 and colony formation assays, respectively. An orthotopic nude mouse model was used to evaluate tumor growth and therapeutic response in vivo. Potential substrates of RNF146 were screened using the BioGRID database and validated by Western blot analysis. RNF146 expression was significantly reduced in breast cancer tissues, including TNBC, compared with normal tissues, and low RNF146 expression was associated with poor overall survival. RNF146 overexpression markedly enhanced olaparib sensitivity in vitro and significantly inhibited tumor growth while promoting apoptosis in vivo. XRCC5 was identified as a potential substrate of RNF146 and was confirmed to be downregulated by RNF146 both in vitro and in tumor tissues. These findings indicate that RNF146 enhances olaparib sensitivity in TNBC, at least in part, through downregulation of XRCC5, and suggest that RNF146 may serve as a prognostic biomarker and a potential therapeutic target for improving PARP inhibitor efficacy in TNBC. - Source: PubMed
Publication date: 2026/03/31
Chen MengTang YezhenXiao TingtingMa HongningSun HuihuiWang ZhijunZhao Wei - Tankyrases (TNKS1 and TNKS2) are multifunctional enzymes of the poly(ADP-ribose) polymerase (PARP) family that regulate cellular homeostasis by catalyzing poly(ADP-ribosyl)ation and stabilizing protein-protein interactions through their ankyrin repeat clusters. By engaging with diverse sets of proteins, TNKSs act as central hubs that coordinate signaling and metabolic pathways. In this review, we discuss how TNKS -protein interactions underpin their roles across multiple biological pathways, including Wnt/β-catenin, YAP and SRC signaling, mTORC1 signaling, DNA damage repair (via PARP crosstalk and recruitment of repair factors), telomere maintenance, cell-cycle regulation, glucose metabolism, cytoskeleton rearrangement, autophagy, proteasomal degradation, and apoptosis. We highlight the structural basis of these interactions, emphasizing ankyrin repeat domain recognition motifs and the consequences of TNKS-mediated PARylation on protein stability and localization. By integrating findings from oncology, virology, and metabolism, we illustrate how TNKS functions as a nodal regulator linking genome stability, signaling fidelity, and metabolic control. The interplay between TNKS and these varied pathways is essential for the well-being of the organism, with its dysregulation having severe biological and clinical consequences, which are discussed here. Finally, we consider therapeutic implications of disrupting TNKS-protein interactions, with particular attention paid to selective small-molecule inhibitors and their translational potential in cancer, viral infections, and degenerative diseases. - Source: PubMed
Publication date: 2026/02/14
Chalabi Hagkarim NafisehGrand Roger J - ADP-ribosylation can occur as mono-ADP-ribose (MAR) or be extended into poly-ADP-ribose (PAR). Tankyrase, a PAR transferase, adds PAR to itself and other proteins targeting them for proteasomal degradation via the PAR-binding E3 ligase RNF146. This degradation can be counteracted by RING-UIM E3 ligases RNF114 and RNF166, although the process is unclear. Here, we identify a mechanism that can regulate the balance between MAR and PAR on tankyrase to control degradation. We show that Deltex E3 ligases DTX2 and DTX3 catalyze monoubiquitylation of tankyrase in cells. This ubiquitylation occurs, not on a (canonical) lysine, but rather on MAR, creating a monoubiquitin-MAR hybrid mark. RNF114 and RNF166 recognize this mark using a unique hybrid reader domain and further diubiquitylate it. This ubiquitylation of MAR, which occurs near the ADP-ribose addition site, prevents PAR formation, antagonizing the action of the PAR-binding E3 ligase RNF146 and stabilizing tankyrase. These findings reveal an interplay between ubiquitin, ADP-ribose, and E3 ligases in cellular signaling. - Source: PubMed
Publication date: 2025/09/03
Perrard JeromeGao KevinRing KatherineSmith Susan