engleski

Telomere Binding Protein TRF1 modulates the kinase activities of Nme1/2

The human Nme1 protein was recognized as the first metastasis suppressor and is the most studied member of Nme (expressed in non-metastatic cell) family of proteins, previously known as nucleoside diphosphate kinase family (Nm23/NDPK). The main characteristic of Nme1 and Nme2 proteins is maintaining the balance of different nucleoside triphosphates by catalyzing the phosphorylation of nucleoside diphosphates. While it is still unclear which biochemical activities are responsible for Nme's antimetastatic role, it is known that both Nme1 and Nme2 proteins interact with TRF1, a telomeric repeat binding factor, thus connecting telomere length alteration (aging) and metastatic progression of cancer cells. The thesis focuses primarily on different levels of NDPK activities in correlation with the interaction of Nme1 and Nme2 with TRF1 protein. Since poly-(ADP-ribosyl)ation has a key role in regulation of important cellular functions carried by TRF1 protein, modulation of kinetic activity of Nme1-TRF1 and Nme2-TRF1 protein by poly-(ADP-ribosyl)ation of TRF1 was studied. Our results showed that the interaction of Nme1/Nme2 with TRF1 protein have a significant impact on their kinase activity. There is also a difference in the activity of the enzymes in complex with the poly(ADP) - ribosylated and unmodified TRF1 protein. Therefore, the changes in protein kinase activity of Nme1/Nme2 proteins indicate potential impact on their functions, such as the suppression of metastasis.

NDPK, telomere, Nme1, Nme2, TRF1

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