PARP1 acetylation at K119 is essential in regulating the progression and proliferation of cervical cancer cells.

Autor: Yang, Li-Li, Zhang, Xue-Ke, Cao, Ying, Shi, Li-Ya, Xie, Shi-Ya, Yang, Yan-Jie, Wu, Shao-Jun, Sun, Hong-Zhan, Tang, Xue-Jun, Yuan, Dong-Lan, Zhang, Dong, Xu, Xiao-Feng, Li, Qian, Ying, Xiao-Yan
Zdroj: Medical Oncology; Nov2024, Vol. 41 Issue 11, p1-11, 11p
Abstrakt: Cervical cancer, CC, is one of the malignant cancers in women worldwide. Many studies about the genesis and progression of CC have been done at genomic, transcriptional, translational, and epigenetic levels. However, much less is done at post-translational modification (PTM) level. We first used pan-PTM antibodies to compare the pan PTM levels between clinical normal cervical tissues and CC tissues; we then sent the selected samples for label-free identification of acetylation sites. Next, we employed WT or K119A mutant PARP1-EGFP-STREPII plasmid transfection in Hela cells and examined various indexes including colony formation, wound healing, ROS generation, early apoptosis, and immunofluorescence and quantification of proliferation markers (Ki67, PCNA, and p-P53). Last, we examined the levels of multiple important kinases regulating cervical cancer progression. We found that pan-acetylation was the most downregulated in clinical CC samples, whereas the acetylation of PARP1, Poly(ADP-ribose) polymerase-1, was upregulated at K119. Next, we showed that PARP1-WT overexpression significantly suppressed the proliferation and progression in CC cell line Hela, while K119A overexpression didn't show any impact. Finally, PARP1-WT overexpression significantly decreased p-ERK1/2 while didn't affect the phosphorylation levels of other important kinases such as AKT, MTOR, and RPS6. This study discovered a new type of PTM of PARP1 in CC, and showed that PARP1 acetylation at K119 is essential in regulating the proliferation and progression of CC through ERK1/2. Further studies are required to investigate how PARP1 acetylation impact its function. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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