Embryonic Stem Cell-Expressed RAS, A Novel Member Of The RAS Family, Modulates Maintenance Of Liver Stem Cells AndSurvival Of Cancer Cells

Publish Year: 1395
نوع سند: مقاله کنفرانسی
زبان: English
View: 481

نسخه کامل این Paper ارائه نشده است و در دسترس نمی باشد

  • Certificate
  • من نویسنده این مقاله هستم

این Paper در بخشهای موضوعی زیر دسته بندی شده است:

استخراج به نرم افزارهای پژوهشی:

لینک ثابت به این Paper:

شناسه ملی سند علمی:

NASTARANCANSER02_016

تاریخ نمایه سازی: 22 دی 1396

Abstract:

RAS proteins are central components of intracellular signaling pathways. Somatic mutations havebeen identified in 1/3 of human tumors, for example 90%, 50%, 30% and 25% of pancreatic, colorectal,lung and melanoma carcinoma, respectively. Oncogenic activation of three closely related membersof RAS family (HRAS, KRAS and NRAS) is mainly due to somatic point mutations in codon 12, 13 and61. These mutations render RAS protein in its active form that contributes to cell proliferation andanti-apoptosis. However, they are also important for embryo development. Germline mutations ofRAS family members and their signaling components causes a cluster of genetic disorderscollectively called RASophathy. A novel member of this family, embryonic stem cell-expressed RAS(ERAS), has deviation at codon 12 (HRAS numbering) resulting in a constitutive active protein. ERASis not regulated at the protein level by GTPase activating proteins (GAPs) but rather at thetranscriptional levels through the DNA methylation. Unlike classical RAS isoforms (HRAS, NRASand KRAS), ERAS harbors an extended N-terminus that is important for protein-protein interactionand probably subcellular localization. In addition, we detected ERAS is differentially expressed indifferent human cancer cell lines as well as normal cells of the body, including the hepatic stellatecells. ERAS has a distinct amino acid sequence within its effector binding site that modules itscellular functions, especially by activating the PI3K-AKT-mTOR and HIPPO-MST1/2-YAP axes.

Authors

Saeideh Nakhaei-Rad

Institute Of Biochemistry And Molecular Biology II, Medical Faculty Of The Heinrich-Heine University, Düsseldorf, Germany

Inga Rebecca Heinen

Institute Of Biochemistry And Molecular Biology II, Medical Faculty Of The Heinrich-Heine University, Düsseldorf, Germany

Hossein Nakhaeizadeh

Institute Of Biochemistry And Molecular Biology II, Medical Faculty Of The Heinrich-Heine University, Düsseldorf, Germany

Mohammad R Ahmadian

Institute Of Biochemistry And Molecular Biology II, Medical Faculty Of The Heinrich-Heine University, Düsseldorf, Germany