Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The apoptosis that occurs in the immature testis under physiological conditions is necessary for male germ cell development, whereas improper activation of apoptosis can impair spermatogenesis and cause defects in reproduction. We previously demonstrated that in mice, the makorin-2 (Mkrn 2) gene is expressed exclusively in the testis and its deletion leads to male infertility. To understand the potential molecular mechanism, in this study, we found that levels of apoptosis in the testis were abnormally high in the absence of Mkrn 2. To identify specific gene(s) involved, we performed digital gene expression profiling (DGE) and pathway analysis via gene set enrichment analysis (GSEA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and we found that MKRN2 inhibits p53 apoptosis effector related to PMP22 (PERP) expression and that levels of the protein in sperm samples have an inverse correlation with infertility levels. GSEA additionally indicated that PERP is a negative regulator of spermatogenesis and that its ectopic expression induces male infertility. Further, Gene Expression Omnibus (GEO) dataset analysis showed that p53, upstream of PERP, was upregulated in oligoasthenoteratozoospermia (OAT). These observations suggest that Mkrn 2 is crucial for protecting germ cells from excessive apoptosis and implicate Mkrn 2-based suppression of the p53/PERP signaling pathway in spermatogenesis and male fertility.
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PMID:Mkrn2 deficiency induces teratozoospermia and male infertility through p53/PERP-mediated apoptosis in testis. 3148 47

Melanoma is the most aggressive and lethal type of skin cancer. The aim of the present study was to illustrate the molecular mechanism of makorin ring finger protein 2 (MKRN2) control of melanoma cell proliferation. The expression level of MKRN2 was detected in human malignant melanoma cell lines by immunoblotting and reverse transcription-quantitative PCR. Short hairpin RNAs for MKRN2 were designed and transfected into melanoma cells, and the proliferation of these cells was detected by MTT and colony formation assays. The interaction of MKRN2 with P53 was detected by co-immunoprecipitation and glutathione S-transferase pulldown assays. The ubiquitination of P53 by MKRN2 was detected by in vitro ubiquitination assays. A P53-knockout cell line was generated using the CRISPR-Cas9 method. MKRN2 exhibited higher expression levels in melanoma cells, and downregulation of MKRN2 inhibited melanoma cell growth in a P53-dependent manner. MKRN2 regulated melanoma cell proliferation by interacting and ubiquitylating P53, which suggests that MKRN2 may be a potential therapeutic target for melanoma.
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PMID:Ubiquitination of P53 by E3 ligase MKRN2 promotes melanoma cell proliferation. 3219 92