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  1. Article ; Online: Beyond HAT Adaptor: TRRAP Liaisons with Sp1-Mediated Transcription.

    Yin, Bo-Kun / Wang, Zhao-Qi

    International journal of molecular sciences

    2021  Volume 22, Issue 22

    Abstract: ... transcription. TRRAP, as the only member lacking the enzymatic activity in this family, is an adaptor protein ... The members of the phosphatidylinositol 3-kinase-related kinase (PIKK) family play vital roles ... for several histone acetyltransferase (HAT) complexes and a scaffold protein for multiple transcription factors. TRRAP has been ...

    Abstract The members of the phosphatidylinositol 3-kinase-related kinase (PIKK) family play vital roles in multiple biological processes, including DNA damage response, metabolism, cell growth, mRNA decay, and transcription. TRRAP, as the only member lacking the enzymatic activity in this family, is an adaptor protein for several histone acetyltransferase (HAT) complexes and a scaffold protein for multiple transcription factors. TRRAP has been demonstrated to regulate various cellular functions in cell cycle progression, cell stemness maintenance and differentiation, as well as neural homeostasis. TRRAP is known to be an important orchestrator of many molecular machineries in gene transcription by modulating the activity of some key transcription factors, including E2F1, c-Myc, p53, and recently, Sp1. This review summarizes the biological and biochemical studies on the action mode of TRRAP together with the transcription factors, focusing on how TRRAP-HAT mediates the transactivation of Sp1-governing biological processes, including neurodegeneration.
    MeSH term(s) Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; E2F1 Transcription Factor/genetics ; E2F1 Transcription Factor/metabolism ; Gene Expression Regulation ; Histone Acetyltransferases/genetics ; Histone Acetyltransferases/metabolism ; Humans ; Multienzyme Complexes/genetics ; Multienzyme Complexes/metabolism ; Neurodegenerative Diseases/genetics ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/pathology ; Neurogenesis/genetics ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Protein Binding ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-myc/metabolism ; Signal Transduction ; Sp1 Transcription Factor/genetics ; Sp1 Transcription Factor/metabolism ; Transcription, Genetic ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
    Chemical Substances Adaptor Proteins, Signal Transducing ; E2F1 Transcription Factor ; E2F1 protein, human ; MYC protein, human ; Multienzyme Complexes ; Nuclear Proteins ; Proto-Oncogene Proteins c-myc ; Sp1 Transcription Factor ; SP1 protein, human ; Tumor Suppressor Protein p53 ; transformation-transcription domain-associated protein ; Histone Acetyltransferases (EC 2.3.1.48)
    Language English
    Publishing date 2021-11-18
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms222212445
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Adaptor protein XB130 regulates the aggressiveness of cholangiocarcinoma.

    Poosekeaw, Pirawan / Pairojkul, Chawalit / Sripa, Banchob / Sa Ngiamwibool, Prakasit / Iamsaard, Sitthichai / Sakonsinsiri, Chadamas / Thanan, Raynoo / Ungarreevittaya, Piti

    PloS one

    2021  Volume 16, Issue 11, Page(s) e0259075

    Abstract: ... with distinct pathological features. Adaptor proteins have implicated in cell proliferation, migration, and ... invasion of different cancer cells. The objective of this study was to assess whether the adaptor protein ... Small interfering (si) RNA-mediated XB130 gene silencing was conducted to evaluate the effects ...

    Abstract Cholangiocarcinoma (CCA) is a group of heterogenous malignancies arising from bile duct epithelium with distinct pathological features. Adaptor proteins have implicated in cell proliferation, migration, and invasion of different cancer cells. The objective of this study was to assess whether the adaptor protein XB130 (AFAP1L2) is a critical biological determinant of CCA outcome. XB130 expression levels were investigated in four CCA cell lines compared to an immortalized cholangiocyte cell line by Western blotting. Small interfering (si) RNA-mediated XB130 gene silencing was conducted to evaluate the effects of reduced XB130 expression on cell proliferation, migration, and invasion by MTT, transwell migration and cell invasion assay. The immunohistochemical quantification of XB130 levels were performed in surgically resected formalin-fixed, paraffin-embedded specimens obtained from 151 CCA patients. The relationship between XB130 expression and the clinicopathological parameters of CCA patients were analyzed. Our results showed that XB130 was highly expressed in KKU-213A cell line. Knockdown of XB130 using siRNA significantly decreased the proliferation, migration, and invasion properties of KKU-213A cells through the inhibition of PI3K/Akt pathway, suggesting that XB130 plays an important role in CCA progression. Moreover, elevated XB130 expression levels were positive relationship with lymphovascular space invasion (LVSI), intrahepatic type of CCA, high TNM staging (stage III, IV), high T classification (T3, T4), and lymph node metastasis. We provide the first evidence that the overexpression of XB130 is associated with tumorigenic properties of CCA cells, leading to CCA progression with aggressive clinical outcomes.
    MeSH term(s) Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Adult ; Aged ; Bile Duct Neoplasms/metabolism ; Bile Duct Neoplasms/pathology ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Cell Line, Transformed ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; Cholangiocarcinoma/metabolism ; Cholangiocarcinoma/pathology ; Female ; Gene Knockdown Techniques/methods ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness/genetics ; Neoplasm Staging ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/genetics ; Transfection
    Chemical Substances AFAP1L2 protein, human ; Adaptor Proteins, Signal Transducing ; Biomarkers, Tumor ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
    Language English
    Publishing date 2021-11-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0259075
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Molecular mechanism of XB130 adaptor protein mediates trastuzumab resistance in gastric cancer.

    Yang, Shengnan / Wang, Binbin / Liao, Jiaqi / Hong, Ziyang / Zhong, Xuxian / Chen, Suling / Wu, Ziqing / Zhang, Xingyu / Zuo, Qiang

    Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico

    2022  Volume 25, Issue 3, Page(s) 685–695

    Abstract: ... to further validate the in-vitro results.: Results: The expression of XB130 adaptor protein was remarkably ... pathway through binding to PI3K p85α under the mediation of SRC kinase and regulating PTEN gene transcription, and in turn ... proteins of members has become an important way.: Methods: In this study, western blot, qRT-PCR, CCK8 ...

    Abstract Background: Recent studies have shown that the activation of PI3K/AKT signaling pathway is an essential molecular mechanism participating in trastuzumab resistance in HER2 + GC (gastric cancer). However, how can we effectively inhibit AKT activity associated with drug resistance during trastuzumab treatment? Screening inhibitors against the upstream receptors of PI3K/AKT signaling pathway or interacting proteins of members has become an important way.
    Methods: In this study, western blot, qRT-PCR, CCK8, Co-IP and other techniques were used to explore possible mechanisms participating in trastuzumab resistance in vitro. Besides, the xenograft mouse model and GC tissue samples from patients were used to further validate the in-vitro results.
    Results: The expression of XB130 adaptor protein was remarkably increased in GC cell lines resistant to trastuzumab, and knockdown of XB130 could reverse the resistance via downregulating p-AKT. In addition, p-SRC (Tyr416) was increased in resistant cells, which could facilitate the binding of XB130 to PI3K p85α. It was also discovered that XB130 could negatively regulate PTEN gene transcription, and thus a positive feedback loop was formed between SRC-XB130-PTEN.
    Conclusions: In HER2 + GC, XB130 contributes to trastuzumab resistance by stimulating the PI3K/AKT signaling pathway through binding to PI3K p85α under the mediation of SRC kinase and regulating PTEN gene transcription, and in turn forming a positive feedback loop between SRC-XB130-PTEN.
    MeSH term(s) Humans ; Animals ; Mice ; Trastuzumab/pharmacology ; Trastuzumab/therapeutic use ; Proto-Oncogene Proteins c-akt/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Stomach Neoplasms/drug therapy ; Stomach Neoplasms/genetics ; Stomach Neoplasms/metabolism ; Signal Transduction ; Adaptor Proteins, Signal Transducing/genetics ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; PTEN Phosphohydrolase
    Chemical Substances Trastuzumab (P188ANX8CK) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Adaptor Proteins, Signal Transducing ; PTEN Phosphohydrolase (EC 3.1.3.67)
    Language English
    Publishing date 2022-10-25
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2397359-6
    ISSN 1699-3055 ; 1699-048X
    ISSN (online) 1699-3055
    ISSN 1699-048X
    DOI 10.1007/s12094-022-02974-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The adaptor protein APS modulates BCR signalling in mature B cells.

    Dondi, Elisabetta / Sibarita, Jean-Baptiste / Varin-Blank, Nadine / Velazquez, Laura

    Cellular signalling

    2020  Volume 73, Page(s) 109673

    Abstract: ... of the Lnk/SH2B family of adaptor proteins, showed that this adaptor plays a BCR-mediated regulatory role ... interferes, as a scaffold protein, with the stability of Syk kinase by recruiting Cbl. This function is ... Activation process of mature B cell is predominantly driven by specific BCR-mediated pathways ...

    Abstract Activation process of mature B cell is predominantly driven by specific BCR-mediated pathways, switched on and off all through late B cell differentiation stages. Mice deficient for APS, a member of the Lnk/SH2B family of adaptor proteins, showed that this adaptor plays a BCR-mediated regulatory role in mature B cells. However, the intermediates involved in this adaptor modulating functions in B cells are still unknown. In the present study, we investigated the role of APS in regulating BCR signalling notably through cytoskeleton remodeling in mature B cells. Herein, we showed that APS function is stage specific, as it exclusively intervenes in mature B cells. Upon activation, APS colocalizes with the BCR and associates with important regulators of BCR signalling, such as Syk and Cbl kinase. Importantly, APS interferes, as a scaffold protein, with the stability of Syk kinase by recruiting Cbl. This function is mainly mediated by APS SH2 domain, which regulates BCR-evoked cell dynamics. Our findings thus reveal that APS plays a regulatory role in BCR-induced responses by specifically modulating its interacting partners, which positions APS as a relevant modulator of BCR signalling in mature B cells.
    MeSH term(s) Adaptor Proteins, Signal Transducing/metabolism ; Animals ; B-Lymphocytes/cytology ; B-Lymphocytes/metabolism ; Cell Line ; Mice ; Mice, Inbred C57BL ; Proto-Oncogene Proteins c-bcr/metabolism ; Signal Transduction
    Chemical Substances Adaptor Proteins, Signal Transducing ; Sh2b2 protein, mouse ; Bcr protein, mouse (EC 2.7.11.1) ; Proto-Oncogene Proteins c-bcr (EC 2.7.11.1)
    Language English
    Publishing date 2020-05-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1002702-6
    ISSN 1873-3913 ; 0898-6568
    ISSN (online) 1873-3913
    ISSN 0898-6568
    DOI 10.1016/j.cellsig.2020.109673
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Adaptor protein 3BP2 regulates dectin-1-mediated cellular signalling to induce cytokine expression and NF-κB activation.

    Chihara, Kazuyasu / Chihara, Yuri / Takeuchi, Kenji / Sada, Kiyonao

    The Biochemical journal

    2022  Volume 479, Issue 4, Page(s) 503–523

    Abstract: The adaptor protein c-Abl Src homology 3 domain-binding protein-2 (3BP2) is phosphorylated ... were restored by wild-type 3BP2, suggesting that 3BP2 was involved in the dectin-1-mediated signalling ... mediated by the Fc receptor for IgG. Although it is well established that various phagocytic cells express ...

    Abstract The adaptor protein c-Abl Src homology 3 domain-binding protein-2 (3BP2) is phosphorylated by spleen tyrosine kinase (Syk), and the phosphorylation of Tyr183 is important in the regulation of immune responses. Recently, we reported that 3BP2 plays important roles in phagocytosis and chemokine expression mediated by the Fc receptor for IgG. Although it is well established that various phagocytic cells express Syk-coupled C-type lectin receptors (CLRs) to induce innate immune responses, the functions of 3BP2 and the physiological relevance of the phosphorylation of Tyr183 remain elusive. In this study, we generated genome-edited mice and observed that 3BP2 influenced the development of bone marrow-derived dendritic cells (BMDCs) induced by granulocyte-macrophage colony-stimulating factor. In addition, we found that 3BP2 was critical for cytokine expression induced by Syk-coupled CLRs - dectin-1 and macrophage-inducible C-type lectin. Immunoblotting analyses revealed that 3BP2 was required for the dectin-1-induced activation of NF-κB p65. The impaired expression of cytokines and activation of NF-κB in 3BP2-mutant cells were restored by wild-type 3BP2, suggesting that 3BP2 was involved in the dectin-1-mediated signalling that led to NF-κB activation. Furthermore, we found that the phosphorylation of Tyr183 is not essential for cytokine expression and that 3BP2 in combination with caspase recruitment domain family member 9 activates NF-κB in HEK-293T cells. Collectively, these results indicate that in addition to the development of BMDCs, 3BP2 plays an important role in the dectin-1-induced activation of NF-κB and cytokine expression.
    MeSH term(s) Adaptor Proteins, Signal Transducing ; Animals ; Cytokines ; Lectins, C-Type ; Mice ; NF-kappa B ; Signal Transduction
    Chemical Substances Adaptor Proteins, Signal Transducing ; Cytokines ; Lectins, C-Type ; NF-kappa B ; Sh3bp2 protein, mouse ; dectin 1
    Language English
    Publishing date 2022-01-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2969-5
    ISSN 1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
    ISSN (online) 1470-8728
    ISSN 0006-2936 ; 0306-3275 ; 0264-6021
    DOI 10.1042/BCJ20210707
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  6. Article: Adaptor proteins in protein kinase C-mediated signal transduction.

    Schechtman, D / Mochly-Rosen, D

    Oncogene

    2001  Volume 20, Issue 44, Page(s) 6339–6347

    Abstract: ... we describe the role of adaptor proteins in determining the specific function of individual protein kinase C ... for activated C-kinase). The role of RACKs in PKC-mediated signaling was determined using isozyme-specific ... precision by which signaling events occur. Adaptor proteins are key to organizing signaling enzymes near ...

    Abstract Spatial and temporal organization of signal transduction is essential in determining the speed and precision by which signaling events occur. Adaptor proteins are key to organizing signaling enzymes near their select substrates and away from others in order to optimize precision and speed of response. Here, we describe the role of adaptor proteins in determining the specific function of individual protein kinase C (PKC) isozymes. These isozyme-selective proteins were called collectively RACKs (receptors for activated C-kinase). The role of RACKs in PKC-mediated signaling was determined using isozyme-specific inhibitors and activators of the binding of each isozyme to its respective RACK. In addition to anchoring activated PKC isozymes, RACKs anchor other signaling enzymes. RACK1, the anchoring protein for activated betaIIPKC, binds for example, Src tyrosine kinase, integrin, and phosphodiesterase. RACK2, the epsilonPKC-specific RACK, is a coated-vesicle protein and thus is involved in vesicular release and cell-cell communication. Therefore, RACKs are not only adaptors for PKC, but also serve as adaptor proteins for several other signaling enzymes. Because at least some of the proteins that bind to RACKs, including PKC itself, regulate cell growth, modulating their interactions with RACKs may help elucidate signaling pathways leading to carcinogenesis and could result in the identification of novel therapeutic targets.
    MeSH term(s) Animals ; Humans ; Isoenzymes/metabolism ; Models, Biological ; Neoplasms/metabolism ; Neoplasms/prevention & control ; Phosphoric Diester Hydrolases/metabolism ; Protein Binding ; Protein Kinase C/metabolism ; Protein-Tyrosine Kinases/metabolism ; Signal Transduction
    Chemical Substances Isoenzymes ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Protein Kinase C (EC 2.7.11.13) ; Phosphoric Diester Hydrolases (EC 3.1.4.-)
    Language English
    Publishing date 2001-10-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 639046-8
    ISSN 1476-5594 ; 0950-9232
    ISSN (online) 1476-5594
    ISSN 0950-9232
    DOI 10.1038/sj.onc.1204778
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  7. Article ; Online: Proproliferative function of adaptor protein GRB10 in prostate carcinoma.

    Khan, Mohammad Imran / Al Johani, Ahmed / Hamid, Abid / Ateeq, Bushra / Manzar, Nishat / Adhami, Vaqar Mustafa / Lall, Rahul K / Rath, Suvasmita / Sechi, Mario / Siddiqui, Imtiaz Ahmad / Choudhry, Hani / Zamzami, Mazin A / Havighurst, Thomas C / Huang, Wei / Ntambi, James M / Mukhtar, Hasan

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2018  Volume 33, Issue 3, Page(s) 3198–3211

    Abstract: ... A., Havighurst, T. C., Huang, W., Ntambi, J. M., Mukhtar, H. Proproliferatve function of adaptor protein GRB10 ... Growth factor receptor-binding protein 10 (GRB10) is a well-known adaptor protein and a recently ... phosphorylation. In PTEN wild-type PCa, GRB10 overexpression promoted mediated PTEN interaction and degradation ...

    Abstract Growth factor receptor-binding protein 10 (GRB10) is a well-known adaptor protein and a recently identified substrate of the mammalian target of rapamycin (mTOR). Depletion of GRB10 increases insulin sensitivity and overexpression suppresses PI3K/Akt signaling. Because the major reason for the limited efficacy of PI3K/Akt-targeted therapies in prostate cancer (PCa) is loss of mTOR-regulated feedback suppression, it is therefore important to assess the functional importance and regulation of GRB10 under these conditions. On the basis of these background observations, we explored the status and functional impact of GRB10 in PCa and found maximum expression in phosphatase and tensin homolog (PTEN)-deficient PCa. In human PCa samples, GRB10 inversely correlated with PTEN and positively correlated with pAKT levels. Knockdown of GRB10 in nontumorigenic PTEN null mouse embryonic fibroblasts and tumorigenic PCa cell lines reduced Akt phosphorylation and selectively activated a panel of receptor tyrosine kinases. Similarly, overexpression of GRB10 in PTEN wild-type PCa cell lines accelerated tumorigenesis and induced Akt phosphorylation. In PTEN wild-type PCa, GRB10 overexpression promoted mediated PTEN interaction and degradation. PI3K (but not mTOR) inhibitors reduced GRB10 expression, suggesting primarily PI3K-driven regulation of GRB10. In summary, our results suggest that GRB10 acts as a major downstream effector of PI3K and has tumor-promoting effects in prostate cancer.-Khan, M. I., Al Johani, A., Hamid, A., Ateeq, B., Manzar, N., Adhami, V. M., Lall, R. K., Rath, S., Sechi, M., Siddiqui, I. A., Choudhry, H., Zamzami, M. A., Havighurst, T. C., Huang, W., Ntambi, J. M., Mukhtar, H. Proproliferatve function of adaptor protein GRB10 in prostate carcinoma.
    MeSH term(s) Animals ; Carcinogens/antagonists & inhibitors ; Carcinogens/metabolism ; Cell Line, Tumor ; Cell Proliferation/genetics ; Cell Proliferation/physiology ; Fibroblasts/cytology ; Fibroblasts/metabolism ; GRB10 Adaptor Protein/antagonists & inhibitors ; GRB10 Adaptor Protein/genetics ; GRB10 Adaptor Protein/metabolism ; Gene Knockdown Techniques ; Humans ; Male ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice ; Models, Biological ; PTEN Phosphohydrolase/deficiency ; PTEN Phosphohydrolase/genetics ; PTEN Phosphohydrolase/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/pathology ; RNA, Messenger ; Signal Transduction
    Chemical Substances Carcinogens ; GRB10 protein, human ; Grb10 protein, mouse ; RNA, Messenger ; GRB10 Adaptor Protein (151441-47-3) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; PTEN Phosphohydrolase (EC 3.1.3.67) ; PTEN protein, human (EC 3.1.3.67) ; Pten protein, mouse (EC 3.1.3.67)
    Language English
    Publishing date 2018-10-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.201800265RR
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  8. Article ; Online: Overexpression of MicroRNA 142-5p Suppresses the Progression of Cervical Cancer through Targeting Phosphoinositol-3-Kinase Adaptor Protein 1 Expression.

    Guo, Junliang / Tang, Tian / Li, Jinhong / Yang, Yihong / Quan, Yi / Zhang, Long / Huang, Wei / Zhou, Muchuan

    Molecular and cellular biology

    2021  Volume 41, Issue 6, Page(s) e0036320

    Abstract: ... in cervical cancer through mediating the phosphoinositol-3-kinase adaptor protein 1 (PIK3AP1)/PI3K/AKT axis ... 5p in cervical cancer cells downregulated PIK3AP1 and inhibited the PI3K/AKT signaling ... signaling pathway, thus suppressing development of cervical cancer, which presents new targets for the treatment ...

    Abstract The aim of current study was to explore the mechanism of microRNA 142-5p (miR-142-5p) in cervical cancer through mediating the phosphoinositol-3-kinase adaptor protein 1 (PIK3AP1)/PI3K/AKT axis. To this end, reverse transcription-quantitative PCR (RT-qPCR) and Western blot analysis results revealed that miR-142-5p was poorly expressed, whereas PIK3AP1 was highly expressed, in cervical cancer tissues and cells. Furthermore, miR-142-5p was hypermethylated in cervical cancer, as reflected by methylation-specific PCR (MS-PCR) and chromatin immunoprecipitation (ChIP) assessment of enrichment of DNMT1/DNMT3a/DNMT3b in the promoter region of miR-142-5p. A target binding relationship between miR-142-5p and PIK3AP1 was established, showing that miR-142-5p targeted and inhibited the expression of PIK3AP1. Loss- and gain-of-function assays were conducted to determine the roles of miR-142-5p and PIK3AP1 in cervical cancer cells. CCK-8, flow cytometry, and Transwell assay results revealed that overexpression of miR-142-5p in cervical cancer cells downregulated PIK3AP1 and inhibited the PI3K/AKT signaling pathway, leading to reduced proliferation, migration, and invasion capacity of cervical cancer cells but enhanced apoptosis. Collectively, epigenetic regulation of miR-142-5p targeted PIK3AP1 to inactivate the PI3K/AKT signaling pathway, thus suppressing development of cervical cancer, which presents new targets for the treatment of cervical cancer.
    MeSH term(s) Adaptor Proteins, Signal Transducing/antagonists & inhibitors ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Blotting, Western ; Cell Line, Tumor ; Female ; Humans ; Mice, Inbred BALB C ; Proto-Oncogene Proteins c-akt/metabolism ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; Uterine Cervical Neoplasms/genetics ; Uterine Cervical Neoplasms/metabolism ; Mice
    Chemical Substances Adaptor Proteins, Signal Transducing ; PIK3AP1 protein, human ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
    Language English
    Publishing date 2021-05-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 779397-2
    ISSN 1098-5549 ; 0270-7306
    ISSN (online) 1098-5549
    ISSN 0270-7306
    DOI 10.1128/MCB.00363-20
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  9. Article ; Online: The adaptor protein c-Cbl-associated protein (CAP) limits pro-inflammatory cytokine expression by inhibiting the NF-κB pathway.

    Vdovenko, Daria / Bachmann, Marta / Wijnen, Winandus J / Hottiger, Michael O / Eriksson, Urs / Valaperti, Alan

    International immunopharmacology

    2020  Volume 87, Page(s) 106822

    Abstract: ... or ponsin, an adaptor protein of the insulin-signalling pathway, mediates anti-viral and anti ... C-Cbl-associated protein (CAP), also known as Sorbin and SH3 domain-containing protein 1 (Sorbs1 ... expression by suppressing the phosphorylation of Inhibitor of kappa B (IκB) kinase (Iκκ)-α and Iκκ-β and ...

    Abstract C-Cbl-associated protein (CAP), also known as Sorbin and SH3 domain-containing protein 1 (Sorbs1) or ponsin, an adaptor protein of the insulin-signalling pathway, mediates anti-viral and anti-cytotoxic protection in acute viral heart disease. In the present study we describe a novel protective immuno-modulatory function of CAP in inflammation. Among the three members of the Sorbs family of adapter molecules, which include CAP (Sorbs1), ArgBP2 (Sorbs2), and Vinexin (Sorbs3), CAP consistently down-regulated the expression of pro-inflammatory cytokines in mouse fibroblasts, cardiomyocytes, and myeloid-derived leukocytes, after Toll-like receptor (TLR) stimulation. Upon the same TLR stimulation, ArgBP2 partially down-regulated pro-inflammatory cytokine production in mouse fibroblasts and cardiomyocytes, while Vinexin rather promoted their production. Mechanistically, CAP limited pro-inflammatory cytokine expression by suppressing the phosphorylation of Inhibitor of kappa B (IκB) kinase (Iκκ)-α and Iκκ-β and their downstream NF-κB-dependent signalling pathway. Molecular affinity between CAP and Iκκ-α/ Iκκ-β was necessary to block the NF-κB pathway. The CAP-dependent inhibitory mechanism - in vivo exclusively IL-6 inhibition - was confirmed after collecting blood from mice with systemic inflammation induced by lipopolysaccharide (LPS) and in the heart tissue collected from mice infected with the cardiotropic Coxsackievirus B3 (CVB3). Taken together, CAP down-regulates pro-inflammatory cytokines by interfering with the normal function of the NF-κB pathway. The promotion of CAP production could support the development of new strategies aiming to limit excessive and detrimental activation of the immune system.
    MeSH term(s) Animals ; Cell Line ; Coxsackievirus Infections/immunology ; Cytokines/immunology ; Enterovirus B, Human ; Fibroblasts ; Humans ; Leukocytes ; Mice, Knockout ; Myocytes, Cardiac ; NF-kappa B/immunology ; Proto-Oncogene Proteins c-cbl/genetics ; Proto-Oncogene Proteins c-cbl/immunology ; Signal Transduction
    Chemical Substances Cytokines ; NF-kappa B ; Proto-Oncogene Proteins c-cbl (EC 2.3.2.27) ; Cbl protein, mouse (EC 6.3.2.-)
    Keywords covid19
    Language English
    Publishing date 2020-07-29
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2043785-7
    ISSN 1878-1705 ; 1567-5769
    ISSN (online) 1878-1705
    ISSN 1567-5769
    DOI 10.1016/j.intimp.2020.106822
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  10. Article ; Online: The adaptor protein Crk in immune response.

    Liu, Dongfang

    Immunology and cell biology

    2013  Volume 92, Issue 1, Page(s) 80–89

    Abstract: The adaptor proteins Crk (CT10 (chicken tumor virus number 10) regulator of kinase), including CrkI ... that Crk proteins function as critical signal molecules in regulating immune cell functions. Emerging data ... on the roles of Crk in activation and inhibitory immunoreceptor signaling suggest that Crk proteins are ...

    Abstract The adaptor proteins Crk (CT10 (chicken tumor virus number 10) regulator of kinase), including CrkI, CrkII and Crk-like, are important signal molecules that regulate a variety of cellular processes. Considerable progress has been made in understanding the roles of the Crk family proteins in signal transduction, with a focus on cellular transformation and differentiation. However, since Crk was identified in 1988, very few studies have addressed how Crk regulates the immune response. Recent work demonstrates that Crk proteins function as critical signal molecules in regulating immune cell functions. Emerging data on the roles of Crk in activation and inhibitory immunoreceptor signaling suggest that Crk proteins are potential immunotherapeutic targets in cancer and infectious diseases. The aim of this review is to summarize recent key findings regarding the role of Crk in immune responses mediated by T, B and natural killer (NK) cells. In particular, the roles of Crk in NK cell functions are discussed.
    MeSH term(s) Animals ; Humans ; Immunity, Cellular/immunology ; Killer Cells, Natural/immunology ; Proto-Oncogene Proteins c-crk/immunology
    Chemical Substances Proto-Oncogene Proteins c-crk
    Language English
    Publishing date 2013-10-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 284057-1
    ISSN 1440-1711 ; 0818-9641
    ISSN (online) 1440-1711
    ISSN 0818-9641
    DOI 10.1038/icb.2013.64
    Database MEDical Literature Analysis and Retrieval System OnLINE

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