Unit:
Τομέας Φυσιολογίας Ζώων και ΑνθρώπουLibrary of the School of Science
Author:
Τσιώρας Κωνσταντίνος
Dissertation committee:
Δρ. Σπύρος Ευθυμιόπουλος Καθηγητής ΕΚΠΑ (Επιβλέπων), Δρ. Αικατερίνη Γαϊτανάκη Καθηγήτρια ΕΚΠΑ, Δρ. Ρεβέκκα Μάτσα-Ερευνήτρια Α΄Ελληνικό Ινστιτούτο Παστέρ
Original Title:
Μονοπάτια σηματοδότησης στα οποία συμμετέχει η νευροειδική πρωτεΐνη ΒΜ88/Cend1
Translated title:
Signaling pathways involving neuronal specific protein BM88/Cend1
Summary:
BM88/Cend1 is a neuronal-lineage specific modulator with a pivotal role in
coordination of cell cycle exit and differentiation of neuronal precursors. In
the current study we identified the signal transduction scaffolding protein
RanBPM as a BM88/Cend1 binding partner and showed that BM88/Cend1, RanBPM and
the dual specificity tyrosine-phosphorylation regulated kinase 1B (Dyrk1B) are
expressed in mouse brain as well as in cultured embryonic cortical neurons
while RanBPM can form complexes with either of the two other proteins. To
elucidate a potential mechanism involving BM88/Cend1, RanBPM and Dyrk1B in cell
cycle progression/exit, we transiently co-expressed these proteins in mouse
neuroblastoma Neuro-2a cells. We found that the BM88/Cend1-dependent or
Dyrk1B-dependent down-regulation of cyclin D1 is reversed following their
functional interaction with RanBPM. When all three proteins are co-expressed,
Dyrk1B is rescued in the nucleus to target cyclin D1 and exert its
antiproliferative function. Additionally, co-expression of RanBPM with either
BM88/Cend1 or Dyrk1B also had a negative effect on Neuro-2a cell
differentiation. Our results suggest that functional interactions between
BM88/Cend1, RanBPM and Dyrk1B affect the balance between cellular proliferation
and differentiation in Neuro-2a cells and indicate that a potentially similar
mechanism may influence cell cycle progression/exit and differentiation of
neuronal precursors.
Keywords:
Cell cycle, Proliferation, Neuronal differentiation, Cyclin D1, Functional interactions
Number of references:
181
