c-Abl tyrosine kinase interacts with MAVS and regulates innate immune response

The tyrosine kinase, c-Abl, plays important roles in many aspects of cellular function. Previous reports showed that c-Abl is involved in NF-κB signaling. However, the functions of c-Abl in innate immunity are still unknown. Here we demonstrate that the mitochondrial antiviral signaling (MAVS) protein can be physically associated with c-Abl in vivo and in vitro. MAVS interacted with c-Abl through its Card and TM domain. A phosphotyrosine-specific antibody indicated that MAVS was phosphorylated by c-Abl. Functional impairment of c-Abl attenuated MAVS or VSV induced type-I IFN production. Importantly, c-Abl knockdown in MCF7 cells displayed impaired MAVS-mediated NF-κB and IRF3 activation. Taken together, our results suggest that c-Abl modulates innate immune response through MAVS.

Structured summary

MINT-7297498, MINT-7297511, MINT-7297557, MINT-7297574: MAVS (uniprotkb:Q7Z434) physically interacts (MI:0915) with c-Abl (uniprotkb:P00519) by anti tag coimmunoprecipitation (MI:0007)MINT-7297542: c-Abl (uniprotkb:P00519) physically interacts (MI:0915) with MAVS (uniprotkb:Q7Z434) by anti bait coimmunoprecipitation (MI:0006)MINT-7297526: c-Abl (uniprotkb:P00519) physically interacts (MI:0915) with MAVS (uniprotkb:Q7Z434) by far western blotting (MI:0047)     

MCL-1ES, a novel variant of MCL-1, associates with MCL-1L and induces mitochondrial cell death

Myeloid cell leukemia-1 (MCL-1L) is a pro-survival member of the BCL-2 family that promotes cell survival. In this study, we identify a new splicing variant of human MCL-1 that encodes MCL-1ES (extra short). Sequence analysis indicates that this variant results from splicing within the first coding exon of MCL-1 at a non-canonical GC-AG donor-acceptor pair. The deduced sequence of MCL-1ES encodes a protein of 197 amino acids, and the PEST (proline, glutamic acid, serine, and threonine) motifs present in MCL-1L are absent. MCL-1ES interacts with MCL-1L and induces mitochondrial cell death, suggesting that alternative splicing of MCL-1 may control the fate of cells.

Structured summary

MINT-7255705, MINT-7255718, MINT-7255731, MINT-7255743:MCL1-ES (uniprotkb:Q07820-2) physically interacts (MI:0914) with MCL1-1L (uniprotkb:Q07820-1) by anti tag coimmunoprecipitation (MI:0007)MINT-7255771:MCL1-ES (uniprotkb:Q07820-2) physically interacts (MI:0914) with Beta actin (uniprotkb:P60709) by anti tag coimmunoprecipitation (MI:0007)MINT-7255781:MCL1-ES (uniprotkb:Q07820-2) physically interacts (MI:0914) with GAPDH (uniprotkb:P04406) by anti tag coimmunoprecipitation (MI:0007)MINT-7255756:MCL1-ES (uniprotkb:Q07820-2) physically interacts (MI:0914) with COX IV (uniprotkb:P13073) by anti tag coimmunoprecipitation (MI:0007)     

S100 proteins regulate the interaction of Hsp90 with Cyclophilin 40 and FKBP52 through their tetratricopeptide repeats

S100 proteins are a subfamily of the EF-hand type calcium sensing proteins, the exact biological functions of which have not been clarified yet. In this work, we have identified Cyclophilin 40 (CyP40) and FKBP52 (called immunophilins) as novel targets of S100 proteins. These immunophilins contain a tetratricopeptide repeat (TPR) domain for Hsp90 binding. Using glutathione-S transferase pull-down assays and immunoprecipitation, we have demonstrated that S100A1 and S100A2 specifically interact with the TPR domains of FKBP52 and CyP40 in a Ca²⁺-dependent manner, and lead to inhibition of the CyP40-Hsp90 and FKBP52-Hsp90 interactions. These findings have suggested that the Ca²⁺/S100 proteins are TPR-targeting regulators of the immunophilins-Hsp90 complex formations.

Structured summary

MINT-7710442: FKBP52 (uniprotkb:Q02790) physically interacts (MI:0915) with S100A6 (uniprotkb:P06703) by competition binding (MI:0405)MINT-7710192: Cyp40 (uniprotkb:P26882) binds (MI:0407) to S100A1 (uniprotkb:P35467) by pull down (MI:0096)MINT-7710412: Cyp40 (uniprotkb:P26882) physically interacts (MI:0915) with S100A2 (uniprotkb:P29034) by competition binding (MI:0405)MINT-7710374: FKBP52 (uniprotkb:Q02790) binds (MI:0407) to S100A2 (uniprotkb:P29034) by pull down (MI:0096)MINT-7710452: Cyp40 (uniprotkb:P26882) physically interacts (MI:0914) with S100A2 (uniprotkb:P29034) and Hsp90 (uniprotkb:P07900) by anti tag coimmunoprecipitation (MI:0007)MINT-7710387: FKBP52 (uniprotkb:Q02790) binds (MI:0407) to S100A6 (uniprotkb:P06703) by pull down (MI:0096)MINT-7710279: FKBP52 (uniprotkb:Q02790) physically interacts (MI:0915) with S100A1 (uniprotkb:P35467) by competition binding (MI:0405)MINT-7710224: FKBP52 (uniprotkb:Q02790) binds (MI:0407) to Hsp90 (uniprotkb:P07900) by pull down (MI:0096)MINT-7710464: Cyp40 (uniprotkb:P26882) physically interacts (MI:0914) with S100A6 (uniprotkb:P06703) and Hsp90 (uniprotkb:P07900) by anti tag coimmunoprecipitation (MI:0007)MINT-7710249: Cyp40 (uniprotkb:P26882) binds (MI:0407) to Hsp90 (uniprotkb:P07900) by pull down (MI:0096)MINT-7710422: Cyp40 (uniprotkb:P26882) physically interacts (MI:0915) with S100A6 (uniprotkb:P06703) by competition binding (MI:0405)MINT-7710348: Cyp40 (uniprotkb:P26882) binds (MI:0407) to S100A2 (uniprotkb:P29034) by pull down (MI:0096)MINT-7710208: FKBP52 (uniprotkb:Q02790) binds (MI:0407) to S100A1 (uniprotkb:P35467) by pull down (MI:0096)MINT-7710265: Cyp40 (uniprotkb:P26882) physically interacts (MI:0915) with S100A1 (uniprotkb:P35467) by competition binding (MI:0405)MINT-7710361: Cyp40 (uniprotkb:P26882) binds (MI:0407) to S100A6 (uniprotkb:P06703) by pull down (MI:0096)MINT-7710476: FKBP52 (uniprotkb:Q02790) physically interacts (MI:0914) with S100A2 (uniprotkb:P29034) and Hsp90 (uniprotkb:P07900) by anti tag coimmunoprecipitation (MI:0007)MINT-7710316: FKBP52 (uniprotkb:Q02790) physically interacts (MI:0914) with S100A1 (uniprotkb:P35467) and Hsp90 (uniprotkb:P07900) by anti tag coimmunoprecipitation (MI:0007)MINT-7710432: FKBP52 (uniprotkb:Q02790) physically interacts (MI:0915) with S100A2 (uniprotkb:P29034) by competition binding (MI:0405)MINT-7710488: FKBP52 (uniprotkb:Q02790) physically interacts (MI:0914) with S100A6 (uniprotkb:P06703) and Hsp90 (uniprotkb:P07900) by anti tag coimmunoprecipitation (MI:0007)MINT-7710329: S100A6 (uniprotkb:P14069) physically interacts (MI:0914) with FKBP52 (uniprotkb:P30416) and Cyp40 (uniprotkb:Q08752) by anti bait coimmunoprecipitation (MI:0006)MINT-7710295: Cyp40 (uniprotkb:P26882) physically interacts (MI:0914) with Hsp90 (uniprotkb:P07900) and S100A1 (uniprotkb:P35467) by anti tag coimmunoprecipitation (MI:0007)     

NMDA receptors interact with flotillin-1 and -2, lipid raft-associated proteins

N-methyl-d-aspartate receptors (NMDARs) mediate excitatory synaptic transmission in the brain. Here we demonstrate interactions between the NR2A and NR2B subunits of NMDARs with flotillin-1 (flot-1), a lipid raft-associated protein. When mapped, analogous regions in the far distal C-termini of NR2A and NR2B mediate binding to flot-1, and the prohibitin homology domain of flot-1 contains binding sites for NR2A and NR2B. Although NR2B can also directly bind to flot-2 via a separate region of its distal C-terminus, NMDARs were significantly more colocalized with flot-1 than flot-2 in cultured hippocampal neurons. Overall, this study defines a novel interaction between NMDARs and flotillins.

Structured summary

MINT-7013094: NR2A (uniprotkb:Q00959), NR2B (uniprotkb:Q00960) and Flot2 (uniprotkb:Q9Z2S9) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-7013147: Flot1 (uniprotkb:Q9Z1E1) physically interacts (MI:0218) with NR2A (uniprotkb:Q00959) by anti bait coimmunoprecipitation (MI:0006)MINT-7013189: Flot1 (uniprotkb:Q9Z1E1) physically interacts (MI:0218) with Flot2 (uniprotkb:Q9Z2S9) by anti bait coimmunoprecipitation (MI:0006)MINT-7013033: NR2A (uniprotkb:Q00959) physically interacts (MI:0218) with Flot1 (uniprotkb:Q9Z1E1) by two hybrid (MI:0018)MINT-7013178: NR1 (uniprotkb:P35439) physically interacts (MI:0218) with Flot2 (uniprotkb:Q9Z2S9) by anti bait coimmunoprecipitation (MI:0006)MINT-7013197, MINT-7013210: NR2B (uniprotkb:Q00960) and NR2A (uniprotkb:Q00959) physically interact (MI:0218) with Flot2 (uniprotkb:Q9Z2S9) by anti bait coimmunoprecipitation (MI:0006)MINT-7013002: NR2B (uniprotkb:Q00960) physically interacts (MI:0218) with Flot1 (uniprotkb:O08917) by two hybrid (MI:0018)MINT-7013117: Flot1 (uniprotkb:Q9Z1E1), NR2B (uniprotkb:Q00960) and NR2A (uniprotkb:Q00959) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-7013171: NR1 (uniprotkb:P35439) physically interacts (MI:0218) with Flot1 (uniprotkb:Q9Z1E1) by anti bait coimmunoprecipitation (MI:0006)MINT-7013017: NR2A (uniprotkb:Q00959) physically interacts (MI:0218) with Flot1 (uniprotkb:O08917) by two hybrid (MI:0018)MINT-7013054: NR2B (uniprotkb:Q00960) physically interacts (MI:0218) with Flot1 (uniprotkb:Q9Z1E1) by two hybrid (MI:0018)MINT-7013129: Flot1 (uniprotkb:Q9Z1E1) physically interacts (MI:0218) with NR2B (uniprotkb:Q00960) by anti bait coimmunoprecipitation (MI:0006)MINT-7013155: NR1 (uniprotkb:P35439) physically interacts (MI:0218) with NR2B (uniprotkb:Q00960) by anti bait coimmunoprecipitation (MI:0006)MINT-7013074: NR2B (uniprotkb:Q00960) physically interacts (MI:0218) with Flot2 (uniprotkb:Q9Z2S9) by two hybrid (MI:0018)MINT-7013162: NR1 (uniprotkb:P35439) physically interacts (MI:0218) with NR2A (uniprotkb:Q00959) by anti bait coimmunoprecipitation (MI:0006)     

MCC, a new interacting protein for Scrib, is required for cell migration in epithelial cells

To further characterize the molecular events supporting the tumor suppressor activity of Scrib in mammals, we aim to identify new binding partners. We isolated MCC, a recently identified binding partner for β-catenin, as a new interacting protein for Scrib. MCC interacts with both Scrib and the NHERF1/NHERF2/Ezrin complex in a PDZ-dependent manner. In T47D cells, MCC and Scrib proteins colocalize at the cell membrane and reduced expression of MCC results in impaired cell migration. By contrast to Scrib, MCC inhibits cell directed migration independently of Rac1, Cdc42 and PAK activation. Altogether, these results identify MCC as a potential scaffold protein regulating cell movement and able to bind Scrib, β-catenin and NHERF1/2.

Structured summary

MINT-7211022: SCRIB (uniprotkb:Q14160) and MCC (uniprotkb:P23508) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-7210609: SCRIB (uniprotkb:Q14160) physically interacts (MI:0915) with MCC (uniprotkb:P23508) by two hybrid (MI:0018)MINT-7210759, MINT-7210792: SCRIB (uniprotkb:Q14160) physically interacts (MI:0914) with PIX beta (uniprotkb:Q14155) by pull down (MI:0096)MINT-7210883, MINT-7210820: SCRIB (uniprotkb:Q14160) physically interacts (MI:0914) with MCC (uniprotkb:P23508) by anti bait coimmunoprecipitation (MI:0006)MINT-7210634, MINT-7210690, MINT-7210731: SCRIB (uniprotkb:Q14160) physically interacts (MI:0914) with MCC (uniprotkb:P23508) by pull down (MI:0096)MINT-7211267: E6 (uniprotkb:P06463) physically interacts (MI:0915) with SCRIB (uniprotkb:Q14160), SNX27 (uniprotkb:Q96L92), UTRN (uniprotkb:P46939), CASK (uniprotkb:O14936), DMD (uniprotkb:P11532) and Dlg (uniprotkb:Q12959) by pull down (MI:0096)MINT-7211237: MCC (uniprotkb:P23508) physically interacts (MI:0915) with SCRIB (uniprotkb:Q14160), EZR (uniprotkb:P15311), SNX27 (uniprotkb:Q96L92), NHERF1 (uniprotkb:O14745) and NHERF2 (uniprotkb:Q15599) by pull down (MI:0096)     

Bag-1M inhibits the transactivation of the glucocorticoid receptor via recruitment of corepressors

The Bcl-2 associated athanogene 1M (Bag-1M) is known to repress the transactivation of the glucocorticoid receptor (GR). We report here that Bag-1M inhibits the action of GR via recruitment of corepressors, including nuclear receptor corepressor (NcoR) and silencing mediator for retinoic acid and thyroid hormone receptor (SMRT), and histone deacetylase (HDAC)3 to the genomic response element of a glucocorticoid-regulated human metallothionein IIa (hMTIIa) gene. A mutant GR lacking the interaction with BAG-1M fails to recruit the corepressors NcoR and SMRT. RNAi-mediated knock down of corepressors and the use of HDAC inhibitor relieved Bag-1M-induced repression on the transactivation of the GR. In addition, Bag-1M is not involved in the degradation of the receptor. These findings indicate a novel mechanism by which Bag-1M acts as a corepressor and downregulates the activity of the GR.

Structured summary

MINT-7216164: HDAC3 (uniprotkb:O15379) physically interacts (MI:0914) with Bag1 (uniprotkb:Q99933) by anti bait coimmunoprecipitation (MI:0006)MINT-7216183: NCOR (uniprotkb:O75376) physically interacts (MI:0914) with Bag1 (uniprotkb:Q99933) by anti bait coimmunoprecipitation (MI:0006)MINT-7216175: SMRT (uniprotkb:Q9Y618) physically interacts (MI:0914) with Bag1 (uniprotkb:Q99933) by anti bait coimmunoprecipitation (MI:0006)     

ARF-dependent regulation of ATM and p53 associated KZNF (Apak) protein activity in response to oncogenic stress

The KRAB-type zinc-finger protein Apak (ATM and p53 associated KZNF protein) specifically suppresses p53-mediated apoptosis. Upon DNA damage, Apak is phosphorylated and inhibited by ATM kinase, resulting in p53 activation. However, how Apak is regulated in response to oncogenic stress remains unknown. Here we show that upon oncogene activation, Apak is inhibited in the tumor suppressor ARF-dependent but ATM-independent manner. Oncogene-induced ARF protein directly interacts with Apak and competes with p53 to bind to Apak, resulting in Apak dissociation from p53. Thus, Apak is differentially regulated in the ARF and ATM-dependent manner in response to oncogenic stress and DNA damage, respectively.

Structured summary

MINT-7989670: p53 (uniprotkb:P04637) binds (MI:0407) to APAK (uniprotkb:Q8TAQ5) by pull down (MI:0096)MINT-7989812: HDM2 (uniprotkb:Q00987) physically interacts (MI:0915) with ARF (uniprotkb:Q8N726-1) by anti bait coimmunoprecipitation (MI:0006)MINT-7989603, MINT-7989626: APAK (uniprotkb:Q8TAQ5) physically interacts (MI:0915) with ARF (uniprotkb:Q8N726-1) by anti bait coimmunoprecipitation (MI:0006)MINT-7989653: ARF (uniprotkb:Q8N726-1) binds (MI:0407) to APAK (uniprotkb:Q8TAQ5) by pull down (MI:0096)MINT-7989686, MINT-7989705, MINT-7989747:APAK (uniprotkb:Q8TAQ5) physically interacts (MI:0915) with ARF (uniprotkb:Q8N726-1) by anti tag coimmunoprecipitation (MI:0007)MINT-7989724: APAK (uniprotkb:Q8TAQ5) physically interacts (MI:0914) with ARF (uniprotkb:Q8N726-1) and p53 (uniprotkb:P04637) by anti tag coimmunoprecipitation (MI:0007)MINT-7989635: ARF (uniprotkb:Q8N726-1) and APAK (uniprotkb:Q8TAQ5) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-7989584, MINT-7989773: APAK (uniprotkb:Q8TAQ5) physically interacts (MI:0915) with p53 (uniprotkb:P04637) by anti tag coimmunoprecipitation (MI:0007)     

Interaction specificity of Arabidopsis 14-3-3 proteins with phototropin receptor kinases

Phototropin receptor kinases play an important role in optimising plant growth in response to blue light. Much is known regarding their photochemical reactivity, yet little progress has been made to identify downstream signalling components. Here, we isolated several interacting proteins for Arabidopsis phototropin 1 (phot1) by yeast two-hybrid screening. These include members of the NPH3/RPT2 (NRL) protein family, proteins associated with vesicle trafficking, and the 14-3-3 lambda (λ) isoform from Arabidopsis. 14-3-3λ and phot1 were found to colocalise and interact in vivo. Moreover, 14-3-3 binding to phot1 was limited to non-epsilon 14-3-3 isoforms and was dependent on key sites of receptor autophosphorylation. No 14-3-3 binding was detected for Arabidopsis phot2, suggesting that 14-3-3 proteins are specific to phot1 signalling.

Structured summary

MINT-7146953: PHOT1 (uniprotkb:O48963) physically interacts (MI:0915) with ARF7 (uniprotkb:Q9LFJ7) by two hybrid (MI:0018)MINT-7147335: PHOT1 (uniprotkb:O48963) physically interacts (MI:0914) with 14-3-3 phi (uniprotkb:P46077) by far Western blotting (MI:0047)MINT-7146854: PHOT1 (uniprotkb:O48963) physically interacts (MI:0915) with RPT2 (uniprotkb:Q682S0) by two hybrid (MI:0018)MINT-7147215: PHOT1 (uniprotkb:O48963) physically interacts (MI:0914) with 14-3-3 lambda (uniprotkb:P48349) by anti tag coimmunoprecipitation (MI:0007)MINT-7147044, MINT-7147185, MINT-7147200, MINT-7147413: PHOT1 (uniprotkb:O48963) physically interacts (MI:0914) with 14-3-3 lambda (uniprotkb:P48349) by far Western blotting (MI:0047)MINT-7146983: PHOT1 (uniprotkb:O48963) physically interacts (MI:0915) with 14-3-3 lambda (uniprotkb:P48349) by two hybrid (MI:0018)MINT-7146871: PHOT1 (uniprotkb:O48963) physically interacts (MI:0915) with NPH3-like (uniprotkb:Q9S9Q9) by two hybrid (MI:0018)MINT-7146905: PHOT1 (uniprotkb:O48963) physically interacts (MI:0915) with ARF2 (uniprotkb:Q9M1P5) by two hybrid (MI:0018)MINT-7147364: PHOT1 (uniprotkb:O48963) physically interacts (MI:0914) with 14-3-3 upsilon (uniprotkb:P42645) by far Western blotting (MI:0047)MINT-7147234: PHOT1 (uniprotkb:O48963) physically interacts (MI:0914) with 14-3-3 kappa (uniprotkb:P48348) by far Western blotting (MI:0047)     

The fast-mobility isoform of mouse Mcl-1 is a mitochondrial matrix-localized protein with attenuated anti-apoptotic activity

The full-length pro-survival protein Mcl-1 predominantly resides on the outer membrane of mitochondria. Here, we identified a mitochondrial matrix-localized isoform of Mcl-1 that lacks 33 amino acid residues at the N-terminus which serve both as a mitochondrial targeting and processing signal. Ectopically-expressed Mcl-1 without the N-terminal 33 residues failed to enter the mitochondrial matrix but retained wt-like activities both for interaction with BH3-only proteins and anti-apoptosis. In contrast, the mitochondrial matrix-localized isoform failed to interact with BH3-only proteins and manifested an attenuated anti-apoptotic activity. This study reveals that import of Mcl-1 into the mitochondrial matrix results in the attenuation of Mcl-1’s anti-apoptotic function.

Structured summary

MINT-7965637: NOXA (uniprotkb:Q9JM54) physically interacts (MI:0915) with Mcl-1 (uniprotkb:P97287) by anti tag coimmunoprecipitation (MI:0007)MINT-7965699: Mcl-1 (uniprotkb:P97287) physically interacts (MI:0915) with Bim (uniprotkb:O43521) by anti bait coimmunoprecipitation (MI:0006)MINT-7965655: Mcl-1 (uniprotkb:P97287) physically interacts (MI:0915) with NOXA (uniprotkb:Q9JM54) by anti bait coimmunoprecipitation (MI:0006)MINT-7965711: Bim (uniprotkb:O43521) physically interacts (MI:0915) with Mcl-1 (uniprotkb:P97287) by anti tag coimmunoprecipitation (MI:0007)MINT-7965673: PUMA (uniprotkb:Q9BXH1) physically interacts (MI:0915) with Mcl-1 (uniprotkb:P97287) by anti tag coimmunoprecipitation (MI:0007)MINT-7965685: Mcl-1 (uniprotkb:P97287) physically interacts (MI:0915) with PUMA (uniprotkb:Q9BXH1) by anti bait coimmunoprecipitation (MI:0006)     

Excitatory amino acid transporter 2 associates with phosphorylated tau and is localized in neurofibrillary tangles of tauopathic brains

Phosphorylated tau (p-tau) is the principal component of neurofibrillary tangles, a pathological hallmark, and likely plays a neurotoxic role in tauopathies including Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). We subjected brains from autopsy cases of AD, PSP, and CBD to a variety of immunohistochemical, immunoblotting, and pull-down assays. In this study, we show that excitatory amino acid transporter 2 (EAAT2) preferentially interacted with phosphorylated tau and was localized in neurofibrillary tangles in the brains of such patients. These results strongly indicate that EAAT2 acts in tauopathy-related neurodegeneration, and abnormalities in glutamate transport play an important role in the pathogenesis of tauopathies.

Structured summary

MINT-7148349, MINT-7148361:TAU (uniprotkb:P10636) physically interacts (MI:0914) with EAAT2 (uniprotkb:P43004) by pull-down (MI:0096)MINT-7148372, MINT-7148384:TAU (uniprotkb:P10636) physically interacts (MI:0914) with EAAT2 (uniprotkb:P43004) by anti bait coimmunoprecipitation (MI:0006)     

Cell cycle regulation of the mammalian CDK activator RINGO/Speedy A

Cell cycle progression is regulated by cyclin-dependent kinases (CDKs), whose activation requires the binding of regulatory subunits named cyclins. RINGO/Speedy A is a mammalian protein that has no amino acid sequence homology with cyclins but can activate CDKs. Here we show that RINGO/Speedy A is a highly unstable protein whose expression and phosphorylation are periodically regulated during the cell cycle. RINGO/Speedy A is degraded by the proteasome and the process involves the ubiquitin ligase SCF^Skp2. Overexpression of a stabilized RINGO/Speedy A form results in the accumulation of high levels of RINGO/Speedy A at late stages of mitosis, which interfere with cytokinesis and chromosome decondensation. Our data show that tight regulation of RINGO/Speedy A is important for the somatic cell cycle.

Structured summary

MINT-7226413:RINGO A (uniprotkb:Q5MJ70) physically interacts (MI:0914) with Ubiquitin (uniprotkb:P62988) by anti bait coimmunoprecipitation (MI:0006)MINT-7226431, MINT-7226448:RINGO A (uniprotkb:Q5MJ70) physically interacts (MI:0914) with Skp2 (uniprotkb:Q13309) by anti tag coimmunoprecipitation (MI:0007)     

Regulation of HOXA2 gene expression by the ATP-dependent chromatin remodeling enzyme CHD8

Chromodomain, helicase, DNA-binding protein 8 (CHD8) is an ATP-dependent chromatin remodeling enzyme that has been demonstrated to exist within a large protein complex which includes WDR5, Ash2L, and RbBP5, members of the Mixed Lineage Leukemia (MLL) histone modifying complexes. Here we show that CHD8 relocalizes to the promoter of the MLL regulated gene HOXA2 upon gene activation. Depletion of CHD8 enhances HOXA2 expression under activating conditions. Furthermore, depletion of CHD8 results in a loss of the WDR5/Ash2L/RbBP5 subcomplex, and consequently H3K4 trimethylation, at the HOXA2 promoter. These studies suggest that CHD8 alters HOXA2 gene expression and regulates the recruitment of chromatin modifying enzymes.

Structured summary

MINT-7542810: CHD8 (uniprotkb:Q9HCK8) physically interacts (MI:0915) with RbBP5 (uniprotkb:Q15291) by anti tag coimmunoprecipitation (MI:0007)MINT-7542794: CHD8 (uniprotkb:Q9HCK8) physically interacts (MI:0915) with WDR5 (uniprotkb:P61964) by anti tag coimmunoprecipitation (MI:0007)MINT-7542820: CHD8 (uniprotkb:Q9HCK8) physically interacts (MI:0915) with ASH2L (uniprotkb:Q9UBL3) by anti tag coimmunoprecipitation (MI:0007)MINT-7542769: CHD8 (uniprotkb:Q9HCK8) physically interacts (MI:0914) with RbBP5 (uniprotkb:Q15291), ASH2L (uniprotkb:Q9UBL3) and WDR5 (uniprotkb:P61964) by anti tag coimmunoprecipitation (MI:0007)     

Coilin interacts with Ku proteins and inhibits in vitro non-homologous DNA end joining

Coilin is a nuclear protein that plays a role in Cajal body formation. The function of nucleoplasmic coilin is unknown. Here we report that coilin interacts with Ku70 and Ku80, which are major players in the DNA repair process. Ku proteins compete with SMN and SmB′ proteins for coilin interaction sites. The binding domain on coilin for Ku proteins cannot be localized to one discrete region, and only full-length coilin is capable of inhibiting in vitro non-homologous DNA end joining (NHEJ). Since Ku proteins do not accumulate in CBs, these findings suggest that nucleoplasmic coilin participates in the regulation of DNA repair.

Structured summary

MINT-8052983:coilin (uniprotkb:P38432) physically interacts (MI:0915) with SmB′ (uniprotkb:P14678) by pull down (MI:0096)MINT-8052941:coilin (uniprotkb:P38432) physically interacts (MI:0915) with Ku70 (uniprotkb:P12956) by competition binding (MI:0405)MINT-8052765:coilin (uniprotkb:P38432) physically interacts (MI:0915) with Ku80 (uniprotkb:P13010) by pull down (MI:0096)MINT-8052971:coilin (uniprotkb:P38432) physically interacts (MI:0915) with SMN (uniprotkb:Q16637) by pull down (MI:0096)MINT-8052957:coilin (uniprotkb:P38432) physically interacts (MI:0915) with Ku80 (uniprotkb:P13010) by competition binding (MI:0405)MINT-8052894, MINT-8052908:coilin (uniprotkb:P38432) binds (MI:0407) to Ku80 (uniprotkb:P13010) by pull down (MI:0096)MINT-8052804:coilin (uniprotkb:P38432) physically interacts (MI:0915) with Ku80 (uniprotkb:P13010) by anti bait coimmunoprecipitation (MI:0006)MINT-8052925:coilin (uniprotkb:P38432) binds (MI:0407) to Ku70 (uniprotkb:P12956) by pull down (MI:0096)MINT-8052786:Ku80 (uniprotkb:P13010) physically interacts (MI:0914) with coilin (uniprotkb:P38432) and Ku70 (uniprotkb:P12956) by anti bait coimmunoprecipitation (MI:0006)MINT-8052776:coilin (uniprotkb:P38432) physically interacts (MI:0915) with Ku70 (uniprotkb:P12956) by pull down (MI:0096)