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Functional Analysis of the 5' Untranslated Region of the PTCH1 gene, transcript variant 1b

Ozretić, Petar (2013) Functional Analysis of the 5' Untranslated Region of the PTCH1 gene, transcript variant 1b. Doctoral thesis, Sveučilište Josipa Jurja Strossmayera u Osijeku, Sveučilišni poslijediplomski interdisciplinarni doktorski studij Molekularne bioznanosti.

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PTCH1 gene is one of the main members of the Hedgehog-Gli signaling pathway. In the 5' untranslated region (5' UTR) of PTCH1 transcript 1b, a CGG-repeat polymorphism was found close to the translation initiation site. Given the role of 5' UTRs in the regulation of translation, our aim was to thoroughly explore all the regulatory elements present in the 5' UTR of PTCH1b. Using luciferase reporter constructs in tests with human cell lines it was shown that the number of CGG repeats has no significant impact on reporter gene expression. The length of 5' UTR was shown to be potentially an important factor in the regulation of PTCH1 expression, for the reason that upstream open reading frames present only in longer 5' UTRs may reduce the amount of Ptch1 protein. The existence of an internal ribosome entry site enables Ptch1 protein synthesis under conditions when the general level of protein synthesis is decreased, such as in low oxygen levels, i.e., hypoxia. All these results point to the exceptionally complex and so far unexplored role of 5' UTR in the regulation of PTCH1 expression.

Item Type: Thesis (Doctoral thesis)
Uncontrolled Keywords: Hedgehog-Gli signaling pathway; PTCH1 gene; 5' untranslated region; CGG repeats; upstream open reading frames; internal ribosome entry site
Subjects: NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology
BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences > Human Genetics, Genomics and Proteomics
Divisions: Division of Molecular Medicine
Project titleProject leaderProject codeProject type
Prijenos signala u tumorima: Hh-Gli put, interakcije i potencijalne terapijeLevanat, Sonja098-0982464-2461MZOS
Depositing User: Petar Ozretić
Date Deposited: 05 Jul 2022 13:15

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