Редактирование: TERF2IP

Telomeric repeat-binding factor 2-interacting protein 1 (TERF2-interacting telomeric protein 1) (TRF2-interacting telomeric protein 1) (Dopamine receptor-interacting protein 5) (Repressor/activator protein 1 homolog) (RAP1 homolog) (hRap1) [DRIP5] [RAP1] [PP8000]

==Publications==

{{medline-entry
|title=Endothelial senescence-associated secretory phenotype (SASP) is regulated by Makorin-1 ubiquitin E3 ligase.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31476350
|abstract=Disturbed flow (d-flow)-induced senescence and activation of endothelial cells (ECs) have been suggested to have critical roles in promoting atherosclerosis. Telomeric repeat-binding factor 2 ([[TERF2]])-interacting protein ([[[[TERF2]]IP]]), a member of the shelterin complex at the telomere, regulates the senescence-associated secretory phenotype (SASP), in which EC activation and senescence are engendered simultaneously by p90RSK-induced phosphorylation of [[[[TERF2]]IP]] S205 and subsequent nuclear export of the [[[[TERF2]]IP]]-[[TERF2]] complex. In this study, we investigated [[[[TERF2]]IP]]-dependent gene expression and its role in regulating d-flow-induced SASP. A principal component analysis and hierarchical clustering were used to identify genes whose expression is regulated by [[[[TERF2]]IP]] in ECs under d-flow conditions. Senescence was determined by reduced telomere length, increased p53 and p21 expression, and increased apoptosis; EC activation was detected by NF-κB activation and the expression of adhesion molecules. The involvement of [[[[TERF2]]IP]] S205 phosphorylation in d-flow-induced SASP was assessed by depletion of [[[[TERF2]]IP]] and mutation of the phosphorylation site. Our unbiased transcriptome analysis showed that [[[[TERF2]]IP]] caused alteration in the expression of a distinct set of genes, including rapamycin-insensitive companion of mTOR ([[RICTOR]]) and makorin-1 ([[MKRN1]]) ubiquitin E3 ligase, under d-flow conditions. In particular, both depletion of [[[[TERF2]]IP]] and overexpression of the [[[[TERF2]]IP]] S205A phosphorylation site mutant in ECs increased the d-flow and p90RSK-induced [[MKRN1]] expression and subsequently inhibited apoptosis, telomere shortening, and NF-κB activation in ECs via suppression of p53, p21, and telomerase (TERT) induction. [[MKRN1]] and [[RICTOR]] belong to a distinct reciprocal gene set that is both negatively and positively regulated by p90RSK. [[[[TERF2]]IP]] S205 phosphorylation, a downstream event of p90RSK activation, uniquely inhibits [[MKRN1]] expression and contributes to EC activation and senescence, which are key events for atherogenesis.
|mesh-terms=* Cellular Senescence
* Endothelial Cells
* Human Umbilical Vein Endothelial Cells
* Humans
* MicroRNAs
* Nerve Tissue Proteins
* Phosphorylation
* Protein Binding
* Rapamycin-Insensitive Companion of mTOR Protein
* Ribonucleoproteins
* Telomeric Repeat Binding Protein 2
* Ubiquitin-Protein Ligases
|keywords=* Inflammation
* MKRN1
* Senescence
* Senescence-associated secretory phenotype (SASP)
* Telomeric repeat binding factor 2-interacting protein (TERF2IP)
* p90RSK
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059097
}}