Редактирование: DHRS2

Dehydrogenase/reductase SDR family member 2, mitochondrial precursor (EC 1.1.1.-) (Dicarbonyl reductase HEP27) (Protein D) (Short chain dehydrogenase/reductase family 25C member 1) [SDR25C1]

==Publications==

{{medline-entry
|title=Acute [[HSF1]] depletion induces cellular senescence through the [[MDM2]]-p53-p21 pathway in human diploid fibroblasts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29632240
|abstract=Heat shock transcription factor 1 ([[HSF1]]) regulates the expression of a wide array of genes, controls the expression of heat shock proteins (HSPs) as well as cell growth. Although acute depletion of [[HSF1]] induces cellular senescence, the underlying mechanisms are poorly understood. Here, we report that [[HSF1]] depletion-induced senescence (HDIS) of human diploid fibroblasts (HDFs) was independent of HSP-mediated proteostasis but dependent on activation of the p53-p21 pathway, partly because of the increased expression of dehydrogenase/reductase 2 ([[DHRS2]]), a putative [[MDM2]] inhibitor. We observed that HDIS occurred without decreased levels of major HSPs or increased proteotoxic stress in HDFs. Additionally, VER155008, an inhibitor of HSP70 family proteins, increased proteotoxicity and suppressed cell growth but failed to induce senescence. Importantly, we found that activation of the p53-p21 pathway resulting from reduced [[MDM2]]-dependent p53 degradation was required for HDIS. Furthermore, we provide evidence that increased [[DHRS2]] expression contributes to p53 stabilization and HDIS. Collectively, our observations uncovered a molecular pathway in which [[HSF1]] depletion-induced [[DHRS2]] expression leads to activation of the [[MDM2]]-p53-p21 pathway required for HDIS.
|mesh-terms=* Cell Line
* Cell Proliferation
* Cellular Senescence
* Diploidy
* Fibroblasts
* HEK293 Cells
* HSP70 Heat-Shock Proteins
* Heat Shock Transcription Factors
* Humans
* Proto-Oncogene Proteins c-mdm2
* Tumor Suppressor Protein p53
|keywords=* Cellular senescence
* DHRS2
* HSF1
* MDM2
* p53 (TP53)
|full-text-url=https://sci-hub.do/10.1242/jcs.210724
}}