ETS1

Protein C-ets-1 is a protein that in humans is encoded by the ETS1 gene. The protein encoded by this gene belongs to the ETS transcription factor family.

Protein C-ets-1 is a protein that in humans is encoded by the ETS1 gene. The protein encoded by this gene belongs to the ETS transcription factor family. ==Interaction with DNA repair promoters and proteins== ===DNA repair promoters=== The messenger RNA and protein levels of DNA repair protein PARP1 are controlled, in part, by the expression level of the ETS1 transcription factor which interacts with multiple ETS1 binding sites in the promoter region of PARP1. The degree to which the ETS1 transcription factor can bind to its binding sites on the PARP1 promoter depends on the methylation status of the CpG islands in the ETS1 binding sites in the PARP1 promoter. If these CpG islands in ETS1 binding sites of the PARP1 promoter are epigenetically hypomethylated, PARP1 is expressed at an elevated level. The high constitutive levels of PARP1 in centenarians, providing more effective DNA repair, is thought to contribute to their unusual longevity. These levels of PARP1 expression are considered to be due to altered epigenetic control of transactivation of PARP1 expression. As shown by Wilson et al., increased ETS1 expression causes about 50 target genes to increase expression, including DNA repair genes MUTYH, BARD1, ERCC1 and XPA. Increased ETS1 expression causes resistance to cell killing by cisplatin, the resistance thought to be partly due to increased expression of DNA repair genes. ===DNA repair protein interactions=== ETS1 functions are regulated by protein – protein interactions. In particular, ETS1 protein interacts with several DNA repair proteins. ETS1 binds with DNA-dependent protein kinase (DNA-PK) [where the DNA-PK complex is made up of DNA-PKcs and DNA repair Ku (protein), and where Ku itself is a heterodimer of two polypeptides, Ku70 (XRCC6) and Ku80 (XRCC5)]. ETS1 interaction with DNA-PK phosphorylates ETS1. Such phosphorylation of ETS1 alters its target gene repertoire. The Ku80 portion of DNA-PK, acting alone, interacts with ETS1 to down-regulate at least one of its transcriptional activities. As shown by Legrand et al., ETS1 protein interacts with PARP1 protein. ETS1 activates PARP1, causing poly ADP-ribosylation of PARP1 itself and of other proteins, even in the absence of nicked DNA. PARP1 (without self- poly ADP-ribosylation), in turn, is needed for activation of the transactivating activity of ETS1 on a tested promoter. Active PARP1 subsequently causes poly ADP-ribosylation of ETS1, and this appears to promote ETS1 ubiquitination and proteasomal degradation, preventing excessive activity of ETS1.

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