کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8323763 | 1539898 | 2014 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Podoplanin is a substrate of presenilin-1/γ-secretase
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کلمات کلیدی
MEFPDPNPodoplaninγ-SecretaseCTFERMEzrin Radixin Moesin - اذرین رادیسین موزینextracellular - خارج سلولیintracellular domain - دامنه درون سلولیICD - دفیبریلاتورهای کاردیوورتر کاشتنیcytoplasmic - سیتوپلاسمیکtransmembrane - فرابنفشC-terminal fragment - قطعه C ترمینالMetalloprotease - متالوپروتئازmouse embryonic fibroblast - موش فیبروبلاست جنینیRIP - پاره کردنProteolytic processing - پردازش پروتئولیتیکPresenilin - پرنسیلینregulated intramembrane proteolysis - پروتئولیز داخل سلولی تنظیم شده است
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Podoplanin (PDPN) is a mucin-like transmembrane glycoprotein that plays an important role in development and cancer. Here, we provide evidence that the intracellular domain (ICD) of podoplanin is released into the cytosol following a sequential proteolytic processing by a metalloprotease and γ-secretase. Western blotting and cell fractionation studies revealed that HEK293T and MDCK cells transfected with an eGFP-tagged podoplanin construct (PDPNeGFP, 50-63 kDa) constitutively express two C-terminal fragments (CTFs): a â¼33 kDa membrane-bound PCTF33, and a â¼29 kDa cytosolic podoplanin ICD (PICD). While pharmacological inhibition of metalloproteases reduced the expression of PCTF33, treatment of cells with γ-secretase inhibitors resulted in enhanced PCTF33 levels. PCTF33 processing by γ-secretase depends on presenilin-1 (PS1) function: cells expressing a dominant negative form of PS1 (PS1 D385N), and mouse embryonic fibroblasts (MEFs) genetically deficient in PS1, but not in PS2, show higher levels of PCTF33 expression with respect to wild-type MEFs. Furthermore, transfection of PS1 deficient MEFs with wild-type PS1 (PS1 wt) decreased PCTF33 levels. N-terminal amino acid sequencing of the affinity purified PICD revealed that the γ-secretase cleavage site was located between valines 150 and 151, but these residues are not critical for proteolysis. We found that podoplanin CTFs are also generated in cells expressing podoplanin mutants harboring heterologous transmembrane regions. Taken together, these results indicate that podoplanin is a novel substrate for PS1/γ-secretase.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 46, January 2014, Pages 68-75
Journal: The International Journal of Biochemistry & Cell Biology - Volume 46, January 2014, Pages 68-75
نویسندگان
Maria M. Yurrita, Beatriz Fernández-Muñoz, Gaelle del Castillo, Ester MartÃn-Villar, Jaime Renart, Miguel Quintanilla,