کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8303651 | 1537946 | 2018 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Threonine 454 phosphorylation in Grainyhead-like 3 is important for its function and regulation by the p38 MAPK pathway
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کلمات کلیدی
CDKCaMKBLNKATF-2DNAPKB-Cell Linkercheckpoint kinase - بازرسی کینازactivating transcription factor 2 - فعال کردن عامل رونویسی 2DNA-dependent protein kinase - وابسته به پروتئین کیناز وابسته به DNAcalcium/calmodulin-dependent protein kinase - پروتئین کیناز وابسته به کلسیم / کلومودولینChk - چاکcasein kinase - کازئین کینازcyclin-dependent kinase - کییناز وابسته به سیکلین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The mammalian Grainyhead-like 3 (GRHL3) transcription factor is essential for epithelial development and plays a protective role against squamous cell carcinoma of the skin and of the oral cavity. A single nucleotide polymorphism (SNP) in GRHL3, rs141193530 (p.P455A), is associated with non-melanoma skin cancer in human patients. Moreover, it is known that this SNP, as well as another variant, rs41268753 (p.T454M), are associated with nonsyndromic cleft palate and that rs41268753 negatively affects GRHL3 transcriptional activity. These SNPs are located in adjacent codons of the GRHL3 gene, and the occurrence of either SNP abolishes a putative threonine-proline phosphorylation motif at T454 in the encoded protein. The role of phosphorylation in regulating mammalian GRHL function is currently unknown. In this work we show that GRHL3 is phosphorylated at several residues in a human keratinocyte cell line, among them at T454. This site is essential for the full transcriptional activity of GRHL3. The T454 residue is phosphorylated by p38 MAPK in vitro and activation of p38 signaling in cells causes an increase in GRHL3 activity. The regulation of GRHL3 function by this pathway is dependent on T454, as the substitution of T454 with methionine inhibits the activation of GRHL3. Taken together, our results show that T454 is one of the phosphorylated residues in GRHL3 in keratinocytes and this residue is important for the upregulation of GRHL3 transcriptional activity by the p38 pathway.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1865, Issue 7, July 2018, Pages 1002-1011
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1865, Issue 7, July 2018, Pages 1002-1011
نویسندگان
Ewa Krzywinska, Marek Dominick Zorawski, Agnieszka Taracha, Grzegorz Kotarba, Agnieszka Kikulska, Michal Mlacki, Katarzyna Kwiatkowska, Tomasz Wilanowski,