Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation

[ { "id": "2500684", "title": "Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex", "abstract": "The tumor suppressor folliculin (FLCN) enables nutrient-dependent activation of the mechanistic target of rapamycin complex 1 (mTORC1) protein kinase via its guanosine triphosphatase (GTPase) activating protein (GAP) activity toward the GTPase RagC. Concomitant with mTORC1 inactivation by starvation, FLCN relocalizes from the cytosol to lysosomes. To determine the lysosomal function of FLCN, we reconstituted the human lysosomal FLCN complex (LFC) containing FLCN, its partner FLCN-interacting protein 2 (FNIP2), and the RagAGDP:RagCGTP GTPases as they exist in the starved state with their lysosomal anchor Ragulator complex and determined its cryo–electron microscopy structure to 3.6 angstroms. The RagC-GAP activity of FLCN was inhibited within the LFC, owing to displacement of a catalytically required arginine in FLCN from the RagC nucleotide. Disassembly of the LFC and release of the RagC-GAP activity of FLCN enabled mTORC1-dependent regulation of the master regulator of lysosomal biogenesis, transcription factor E3, implicating the LFC as a checkpoint in mTORC1 signaling.", "source_url": "https://science.sciencemag.org/content/366/6468/971", "doc_type": 4, "year": 2019, "issue": 6468, "volume": 366, "first_page": 971, "last_page": 977, "citation_count": 12, "reference_count": 18, "venue": { "id": 2110000196, "name": "SCIENCE", "abbr": "" }, "author": [ { "id": 1001667874, "name": "Rosalie E. Lawrence" }, { "id": 1001302795, "name": "Simon A. Fromm" }, { "id": 1002736372, "name": "Yangxue Fu" }, { "id": 1002727335, "name": "Adam L. Yokom" }, { "id": 1002567581, "name": "Do Jin Kim" }, { "id": 1002736373, "name": "Ashley M. Thelen" }, { "id": 1001431270, "name": "Lindsey N. Young" }, { "id": 1001983287, "name": "Chun-Yan Lim" }, { "id": 1002561364, "name": "Avi J. Samelson" }, { "id": 1001199041, "name": "James H. Hurley" }, { "id": 1001207693, "name": "Roberto Zoncu" } ], "field": [ { "id": 2019017121, "name": "Proteasome" }, { "id": 2025095850, "name": "Protein turnover" }, { "id": 2047539462, "name": "Proteostasis" } ], "cite": [ { "name": "GB/T 7714", "text": "Lawrence Rosalie E., Fromm Simon A., Fu Yangxue, et al. Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex[J]. SCIENCE, 2019, 366(6468): 971-977." }, { "name": "MLA", "text": "Lawrence, Rosalie E., et al. \"Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex\" SCIENCE., vol. 366, no. 6468, 2019, pp. 971-977." }, { "name": "APA", "text": "Lawrence Rosalie E., Fromm Simon A., Fu Yangxue, Yokom Adam L., Kim Do Jin, Thelen Ashley M., ... & Hurley James H. (2019). Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex. SCIENCE, 366(6468), 971-977." }, { "name": "BibTeX", "text": "@inproceedings{Acemap2500684,\n title=\"Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex\",\n author=\"{Rosalie E. Lawrence} and {Simon A. Fromm} and Yangxue {Fu} and {Adam L. Yokom} and Do Jin {Kim} and {Ashley M. Thelen} and {Lindsey N. Young} and {Chun-Yan Lim} and {Avi J. Samelson} and {James H. Hurley} and Roberto {Zoncu}\",\n journal=\"SCIENCE\",\n volume=\"366\",\n number=\"6468\",\n pages=\"971--977\",\n url=\"https://www.acemap.info/paper/2500684\",\n year=\"2019\"\n}" } ] }, { "id": "3780510", "title": "A Genetic Variant in Long Non-Coding RNA", "abstract": "Background Recently, several studies have demonstrated that two long non-coding RNAs (lncRNAs), HULC and MALAT1, may participate in hepatocellular carcinoma (HCC) development and progression. However, genetic variations in the two lncRNAs and their associations with HCC susceptibility have not been reported. In this study, we hypothesized that single nucleotide polymorphisms (SNPs) in HULC and MALAT1 may contribute to HCC risk. Methods We conducted a case-control study and genotyped two SNPs, rs7763881 in HULC and rs619586 in MALAT1, in 1300 HBV positive HCC patients, 1344 HBV persistent carriers and 1344 subjects with HBV natural clearance to test the associations between the two SNPs and susceptibility to HCC and HBV chronic infection. Results The variant genotypes of rs7763881 were significantly associated with decreased HCC risk in a dominant genetic model [AC/CC vs. AA: adjusted odds ration (OR) = 0.81, 95% confidence intervals (CIs) = 0.68–0.97, P = 0.022]. Furthermore, the variant genotypes of rs619586 was associated with decreased HCC risk with a borderline significance (AG/GG vs. AA: adjusted OR = 0.81, 95% CIs = 0.65–1.01, P = 0.057). However, no significant association was found between the two SNPs and HBV clearance. Conclusions The variant genotypes of rs7763881 in HULC may contribute to decreased susceptibility to HCC in HBV persistent carriers.", "source_url": "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0035145", "doc_type": 4, "year": 2012, "issue": 4, "volume": 7, "first_page": 0, "last_page": 0, "citation_count": 11, "reference_count": 6, "venue": { "id": 2110000215, "name": "PLOS ONE", "abbr": "" }, "author": [ { "id": 1000415955, "name": "Yao Liu" }, { "id": 1001219659, "name": "Shandong Pan" }, { "id": 1000115795, "name": "Li Liu" }, { "id": 1001422814, "name": "Xiangjun Zhai" }, { "id": 1001422811, "name": "Jibin Liu" }, { "id": 1001333258, "name": "Juan Wen" }, { "id": 1000267261, "name": "Yixin Zhang" }, { "id": 1000232119, "name": "Jianguo Chen" }, { "id": 1000786726, "name": "Hongbing Shen" }, { "id": 1000720317, "name": "Zhibin Hu" } ], "field": [], "cite": [ { "name": "GB/T 7714", "text": "Liu Yao, Pan Shandong, Liu Li, et al. A Genetic Variant in Long Non-Coding RNA[J]. PLOS ONE, 2012, 7(4)." }, { "name": "MLA", "text": "Liu, Yao, et al. \"A Genetic Variant in Long Non-Coding RNA\" PLOS ONE., vol. 7, no. 4, 2012." }, { "name": "APA", "text": "Liu Yao, Pan Shandong, Liu Li, Zhai Xiangjun, Liu Jibin, Wen Juan, ... & Hu Zhibin (2012). A Genetic Variant in Long Non-Coding RNA. PLOS ONE, 7(4)." }, { "name": "BibTeX", "text": "@inproceedings{Acemap3780510,\n title=\"A Genetic Variant in Long Non-Coding RNA\",\n author=\"Yao {Liu} and Shandong {Pan} and Li {Liu} and Xiangjun {Zhai} and Jibin {Liu} and Juan {Wen} and Yixin {Zhang} and Jianguo {Chen} and Hongbing {Shen} and Zhibin {Hu}\",\n journal=\"PLOS ONE\",\n volume=\"7\",\n number=\"4\",\n url=\"https://www.acemap.info/paper/3780510\",\n year=\"2012\"\n}" } ] }, { "id": "2340487", "title": "Nonimmunoglobulin target loci of activation-induced cytidine deaminase (AID) share unique features with immunoglobulin genes", "abstract": "Activation-induced cytidine deaminase (AID) is required for both somatic hypermutation and class-switch recombination in activated B cells. AID is also known to target nonimmunoglobulin genes and introduce mutations or chromosomal translocations, eventually causing tumors. To identify as-yet-unknown AID targets, we screened early AID-induced DNA breaks by using two independent genome-wide approaches. Along with known AID targets, this screen identified a set of unique genes (SNHG3, MALAT1, BCL7A, and CUX1) and confirmed that these loci accumulated mutations as frequently as Ig locus after AID activation. Moreover, these genes share three important characteristics with the Ig gene: translocations in tumors, repetitive sequences, and the epigenetic modification of chromatin by H3K4 trimethylation in the vicinity of cleavage sites.", "source_url": "https://www.pnas.org/content/109/7/2479", "doc_type": 4, "year": 2012, "issue": 7, "volume": 109, "first_page": 2479, "last_page": 2484, "citation_count": 10, "reference_count": 19, "venue": { "id": 2110000201, "name": "PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA", "abbr": "" }, "author": [ { "id": 1002501604, "name": "Lucia Kato" }, { "id": 1002031396, "name": "Nasim A. Begum" }, { "id": 1001222763, "name": "A. Maxwell Burroughs" }, { "id": 1001553160, "name": "Tomomitsu Doi" }, { "id": 1000814103, "name": "Jun Kawai" }, { "id": 1001222780, "name": "Carsten O. Daub" }, { "id": 1001218464, "name": "Takahisa Kawaguchi" }, { "id": 1001201008, "name": "Fumihiko Matsuda" }, { "id": 1001222783, "name": "Yoshihide Hayashizaki" }, { "id": 1001132655, "name": "Tasuku HONJO" } ], "field": [ { "id": 2015533717, "name": "Glomus tumour" }, { "id": 2008621301, "name": "Glomangioma" } ], "cite": [ { "name": "GB/T 7714", "text": "Kato Lucia, Begum Nasim A., Burroughs A. Maxwell, et al. Nonimmunoglobulin target loci of activation-induced cytidine deaminase (AID) share unique features with immunoglobulin genes[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109(7): 2479-2484." }, { "name": "MLA", "text": "Kato, Lucia, et al. \"Nonimmunoglobulin target loci of activation-induced cytidine deaminase (AID) share unique features with immunoglobulin genes\" PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA., vol. 109, no. 7, 2012, pp. 2479-2484." }, { "name": "APA", "text": "Kato Lucia, Begum Nasim A., Burroughs A. Maxwell, Doi Tomomitsu, Kawai Jun, Daub Carsten O., ... & HONJO Tasuku (2012). Nonimmunoglobulin target loci of activation-induced cytidine deaminase (AID) share unique features with immunoglobulin genes. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 109(7), 2479-2484." }, { "name": "BibTeX", "text": "@inproceedings{Acemap2340487,\n title=\"Nonimmunoglobulin target loci of activation-induced cytidine deaminase (AID) share unique features with immunoglobulin genes\",\n author=\"Lucia {Kato} and {Nasim A. Begum} and {A. Maxwell Burroughs} and Tomomitsu {Doi} and Jun {Kawai} and {Carsten O. Daub} and Takahisa {Kawaguchi} and Fumihiko {Matsuda} and Yoshihide {Hayashizaki} and Tasuku {HONJO}\",\n journal=\"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA\",\n volume=\"109\",\n number=\"7\",\n pages=\"2479--2484\",\n url=\"https://www.acemap.info/paper/2340487\",\n year=\"2012\"\n}" } ] }, { "id": "2404044", "title": "Hypoxia-induced transcriptional repression of the melanoma-associated oncogene MITF", "abstract": "Microphthalmia-associated transcription factor (MITF) regulates normal melanocyte development and is also a lineage-selective oncogene implicated in melanoma and clear-cell sarcoma (i.e., melanoma of soft parts). We have observed that MITF expression is potently reduced under hypoxic conditions in primary melanocytes and melanoma and clear cell sarcoma cells through hypoxia inducible factor 1 (HIF1)-mediated induction of the transcriptional repressor differentially expressed in chondrocytes protein 1 (DEC1) (BHLHE40), which subsequently binds and suppresses the promoter of M-MITF (melanocyte-restricted MITF isoform). Correspondingly, hypoxic conditions or HIF1α stabilization achieved by using small-molecule prolyl-hydroxylase inhibitors reduced M-MITF expression, leading to melanoma cell growth arrest that was rescued by ectopic expression of M-MITF in vitro. Prolyl hydroxylase inhibition also potently suppressed melanoma growth in a mouse xenograft model. These studies illuminate a physiologic hypoxia response in pigment cells leading to M-MITF suppression, one that suggests a potential survival advantage mechanism for MITF amplification in metastatic melanoma and offers a small-molecule strategy for suppression of the MITF oncogene in vivo.", "source_url": "https://www.pnas.org/content/108/43/E924", "doc_type": 4, "year": 2011, "issue": 43, "volume": 108, "first_page": 0, "last_page": 0, "citation_count": 6, "reference_count": 9, "venue": { "id": 2110000201, "name": "PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA", "abbr": "" }, "author": [ { "id": 1002645085, "name": "Erez Feige" }, { "id": 1001599459, "name": "Satoru Yokoyama" }, { "id": 1001629648, "name": "Carmit Levy" }, { "id": 1001629647, "name": "Mehdi Khaled" }, { "id": 1001231892, "name": "Vivien Igras" }, { "id": 1001215089, "name": "Richard J. Lin" }, { "id": 1001175122, "name": "Stephen Lee" }, { "id": 1001794950, "name": "Hans R. Widlund" }, { "id": 1001689157, "name": "Scott R. Granter" }, { "id": 1001477594, "name": "Andrew L. Kung" }, { "id": 1000093578, "name": "David E. Fisher" } ], "field": [], "cite": [ { "name": "GB/T 7714", "text": "Feige Erez, Yokoyama Satoru, Levy Carmit, et al. Hypoxia-induced transcriptional repression of the melanoma-associated oncogene MITF[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108(43)." }, { "name": "MLA", "text": "Feige, Erez, et al. \"Hypoxia-induced transcriptional repression of the melanoma-associated oncogene MITF\" PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA., vol. 108, no. 43, 2011." }, { "name": "APA", "text": "Feige Erez, Yokoyama Satoru, Levy Carmit, Khaled Mehdi, Igras Vivien, Lin Richard J., ... & Kung Andrew L. (2011). Hypoxia-induced transcriptional repression of the melanoma-associated oncogene MITF. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 108(43)." }, { "name": "BibTeX", "text": "@inproceedings{Acemap2404044,\n title=\"Hypoxia-induced transcriptional repression of the melanoma-associated oncogene MITF\",\n author=\"Erez {Feige} and Satoru {Yokoyama} and Carmit {Levy} and Mehdi {Khaled} and Vivien {Igras} and {Richard J. Lin} and Stephen {Lee} and {Hans R. Widlund} and {Scott R. Granter} and {Andrew L. Kung} and {David E. Fisher}\",\n journal=\"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA\",\n volume=\"108\",\n number=\"43\",\n url=\"https://www.acemap.info/paper/2404044\",\n year=\"2011\"\n}" } ] }, { "id": "3721771", "title": "Inactivation of the", "abstract": "Background Germline mutations in a tumor suppressor gene FLCN lead to development of fibrofolliculomas, lung cysts and renal cell carcinoma (RCC) in Birt-Hogg-Dubé syndrome. TFE3 is a member of the MiTF/TFE transcription factor family and Xp11.2 translocations found in sporadic RCC involving TFE3 result in gene fusions and overexpression of chimeric fusion proteins that retain the C-terminal DNA binding domain of TFE3. We found that GPNMB expression, which is regulated by MiTF, was greatly elevated in renal cancer cells harboring either TFE3 translocations or FLCN inactivation. Since TFE3 is implicated in RCC, we hypothesized that elevated GPNMB expression was due to increased TFE3 activity resulting from the inactivation of FLCN. Methodology/Principal Findings TFE3 knockdown reduced GPNMB expression in renal cancer cells harboring either TFE3 translocations or FLCN inactivation. Moreover, FLCN knockdown induced GPNMB expression in FLCN-restored renal cancer cells. Conversely, wildtype FLCN suppressed GPNMB expression in FLCN-null cells. FLCN inactivation was correlated with increased TFE3 transcriptional activity accompanied by its nuclear localization as revealed by elevated GPNMB mRNA and protein expression, and predominantly nuclear immunostaining of TFE3 in renal cancer cells, mouse embryo fibroblast cells, mouse kidneys and mouse and human renal tumors. Nuclear localization of TFE3 was associated with TFE3 post-translational modifications including decreased phosphorylation. Conclusions/Significance Increased TFE3 activity is a downstream event induced by FLCN inactivation and is likely to be important for renal tumor development. This study provides an important novel mechanism for induction of TFE3 activity in addition to TFE3 overexpression resulting from Xp11.2 translocations, suggesting that TFE3 may be more broadly involved in tumorigenesis.", "source_url": "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0015793", "doc_type": 4, "year": 2010, "issue": 12, "volume": 5, "first_page": 0, "last_page": 0, "citation_count": 6, "reference_count": 9, "venue": { "id": 2110000215, "name": "PLOS ONE", "abbr": "" }, "author": [ { "id": 1001997286, "name": "Seung Beom Hong" }, { "id": 1003933787, "name": "HyoungBin Oh" }, { "id": 1002644805, "name": "Vladimir A. Valera" }, { "id": 1001883160, "name": "Masaya Baba" }, { "id": 1001785383, "name": "Laura S. Schmidt" }, { "id": 1001364110, "name": "W. Marston Linehan" } ], "field": [ { "id": 2028551339, "name": "OK cells" }, { "id": 2018252668, "name": "Penile cancer" } ], "cite": [ { "name": "GB/T 7714", "text": "Hong Seung Beom, Oh HyoungBin, Valera Vladimir A., et al. Inactivation of the[J]. PLOS ONE, 2010, 5(12)." }, { "name": "MLA", "text": "Hong, Seung Beom, et al. \"Inactivation of the\" PLOS ONE., vol. 5, no. 12, 2010." }, { "name": "APA", "text": "Hong Seung Beom, Oh HyoungBin, Valera Vladimir A., Baba Masaya, Schmidt Laura S., & Linehan W. Marston (2010). Inactivation of the. PLOS ONE, 5(12)." }, { "name": "BibTeX", "text": "@inproceedings{Acemap3721771,\n title=\"Inactivation of the\",\n author=\"Seung Beom {Hong} and HyoungBin {Oh} and {Vladimir A. Valera} and Masaya {Baba} and {Laura S. Schmidt} and {W. Marston Linehan}\",\n journal=\"PLOS ONE\",\n volume=\"5\",\n number=\"12\",\n url=\"https://www.acemap.info/paper/3721771\",\n year=\"2010\"\n}" } ] } ]