TY  - JOUR
TI  - Regulation of E2F1 activity via PKA-mediated phosphorylations
AB  - E2F1 becomes activated during the G1 phase of the cell cycle, and posttranslational modifications modulate its activity.Activation of G-protein coupled receptors (GPCR) by many ligands induces the activation of adenylate cyclases and the production ofcAMP, which activates the PKA enzyme. Activated PKA elicits its biological effect by phosphorylating the target proteins containingserine or threonine amino acids in the RxxS/T motif. Since PKA activation negatively regulates cell proliferation, we thought thatactivated PKA would negatively affect the activity of E2F1. In line with this, when we analyzed the amino acid sequence of E2F1,we found 3 hypothetical consensus PKA phosphorylation sites located at 127-130, 232-235, and 361-364 positions and RYET, RLLS,and RMGS sequences. After showing the binding and phosphorylation of E2F1 by PKA, we converted the codons of Threonine-130,Serine-235, and Serine-364 to Alanine and Glutamic acid codons on the eukaryotic E2F1 expression vector we had previously created.We confirmed the phosphorylation of T130, S235, and S364 by developing monoclonal antibodies against phospho-specific forms ofthese sites and showed that their phosphorylation is cell cycle-dependent. According to our results, PKA-mediated phosphorylation ofE2F1 by PKA inhibits proliferation and glucose uptake and induces caspase-3 activation and senescence.
AU  - tanriover, gamze
AU  - DILMAÇ, SAYRA
AU  - ERTOSUN, Mustafa Gokhan
AU  - Hapil, Fatma Zehra
AU  - KOKSOY, SADI
AU  - ozes, osman nidai
DO  - 10.3906/biy-2003-9
PY  - 2020
JO  - Turkish Journal of Biology
VL  - 44
IS  - 5
SN  - 1300-0152
SP  - 215
EP  - 229
DB  - TRDizin
UR  - http://search/yayin/detay/438470
ER  -