کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5506977 | 1536896 | 2017 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Activation of TPA-response element present in human Lemur Tyrosine Kinase 2 (lmtk2) gene increases its expression
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
ACDAP-1 complexTPA-responsive elementTPA-response elementPKC activationSEAPphorbol 12-myristate 13-acetateGM-CSFCHXPKCAP-1tPASecretory alkaline phosphatase - آلکالین فسفاتاز مخلوطPhorbol ester - افلبل استرactinomycin D - اکتینومایسین DTRE - سهcycloheximide - سیکلوهایسیمیدGranulocyte macrophage colony stimulating factor - عامل تحریک کننده کلون ماکروفاژ گرانولوسیتProtein kinase C - پروتئین کیناز سیPromoter - پروموتر
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Regulatory elements present in the promoter of a gene drive the expression of the gene in response to various stimuli. Lemur Tyrosine Kinase 2 (LMTK2) is a membrane-anchored Serine/Threonine kinase involved in endosomal protein trafficking and androgen signaling amongst other processes. Previous studies have shown this protein to be of therapeutic importance in cystic fibrosis and prostate cancer. However, nothing is known about the endogenous expression of this protein and its regulation. In this study, we analyzed the gene encoding human LMTK2, to look for possible regulatory elements that could affect its expression. Interestingly, the human lmtk2 gene contains a consensus TPA (12- O-Tetradecanoylphorbol-13-acetate)-responsive element (TRE) in the region preceding its start codon. The element with the sequence TGAGTCA modulates LMTK2 expression in response to treatment with TPA, a synthetic Protein Kinase C (PKC) activator. It serves as the binding site for c-Fos, a member of the Activator Protein â1 (AP-1) transcription factor complex, which is transactivated by PKC. We observed that TPA, at low concentrations, increases the promoter activity of LMTK2, which leads to a subsequent increase in the mRNA transcript and protein levels. This modulation occurs through binding of the AP-1 transcription factor complex to the lmtk2 promoter. Thus, our current study has established LMTK2 as a TPA-responsive element-containing gene, which is upregulated downstream of PKC activation. Considering the involvement of LMTK2 in intracellular processes as well as pathological conditions, our findings demonstrate a way to modulate intracellular LMTK2 levels pharmacologically for potentially therapeutic purposes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemistry and Biophysics Reports - Volume 12, December 2017, Pages 140-150
Journal: Biochemistry and Biophysics Reports - Volume 12, December 2017, Pages 140-150
نویسندگان
Isha Dey, Neil A. Bradbury,