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DOI | 10.1126/science.aap8210 |
LZTR1 is a regulator of RAS ubiquitination and signaling | |
Bigenzahn, Johannes W.1; Collie, Giovanna M.2,3; Kartnig, Felix1; Pieraks, Melanie1; Vladimer, Gregory, I1; Heinez, Leonhard X.1; Sedlyarov, Vitaly1; Schischlik, Fiorella1; Fauster, Astrid1,4; Rebsamen, Manuele1; Parapatics, Katja1; Blomen, Vincent A.4; Muller, Andre C.1; Winter, Georg E.1; Kralovics, Robert1,5; Brunlinelkamp, Thijn R.1,4,6,7; Mlodzik, Marek2,3; Superti-Furga, Giulio1,8 | |
2018-12-07 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 362期号:6419页码:1171-+ |
文章类型 | Article |
语种 | 英语 |
国家 | Austria; USA; Netherlands |
英文摘要 | In genetic screens aimed at understanding drug resistance mechanisms in chronic myeloid leukemia cells, inactivation of the cullin 3 adapter protein-encoding leucine zipper-like transcription regulator 1 (LZTR1) gene led to enhanced mitogen-activated protein kinase (MAPK) pathway activity and reduced sensitivity to tyrosine kinase inhibitors. Knockdown of the Drosophila LZTR1 ortholog CG3711 resulted in a Rasdependent gain-of-function phenotype. Endogenous human LZTR1 associates with the main RAS isoforms. Inactivation of LZTR1 led to decreased ubiquitination and enhanced plasma membrane localization of endogenous KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog). We propose that LZTR1 acts as a conserved regulator of RAS ubiquitination and MAPK pathway activation. Because LZTR1 disease mutations failed to revert loss-of-function phenotypes, our findings provide a molecular rationale for LZTR1 involvement in a variety of inherited and acquired human disorders. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000452506300059 |
WOS关键词 | VIRUS ENTRY REQUIRES ; GENOMIC ALTERATIONS ; DROSOPHILA EYE ; PROTEIN ; GENE ; CRISPR-CAS9 ; INFORMATION ; LANDSCAPE ; RECEPTOR ; VECTORS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/200253 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1090 Vienna, Austria; 2.Icahn Sch Med Mt Sinai, Dept Cell Dev & Regenerat Biol, 1 Gustave L Levy Pl, New York, NY 10029 USA; 3.Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, 1 Gustave L Levy Pl, New York, NY 10029 USA; 4.Netherlancs Canc Inst, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands; 5.Med Univ Vienna, Dept Lab Med, A-1090 Vienna, Austria; 6.Netherlands Canc Inst, Div Biochem, Oncode Inst, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands; 7.Canc Genom Ctr CGC Nl, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands; 8.Med Univ Vienna, Ctr Physiol & Pharmacol, A-1090 Vienna, Austria |
推荐引用方式 GB/T 7714 | Bigenzahn, Johannes W.,Collie, Giovanna M.,Kartnig, Felix,et al. LZTR1 is a regulator of RAS ubiquitination and signaling[J]. SCIENCE,2018,362(6419):1171-+. |
APA | Bigenzahn, Johannes W..,Collie, Giovanna M..,Kartnig, Felix.,Pieraks, Melanie.,Vladimer, Gregory, I.,...&Superti-Furga, Giulio.(2018).LZTR1 is a regulator of RAS ubiquitination and signaling.SCIENCE,362(6419),1171-+. |
MLA | Bigenzahn, Johannes W.,et al."LZTR1 is a regulator of RAS ubiquitination and signaling".SCIENCE 362.6419(2018):1171-+. |
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