TYR
Tyrosinase precursor (EC 1.14.18.1) (LB24-AB) (Monophenol monooxygenase) (SK29-AB) (Tumor rejection antigen AB)
Publications[править]
Microphthalmia-associated transcription factor (MITF) plays a crucial role in the melanogenesis and proliferation of melanocytes that is dependent on its abundance and modification. Here, we report that epidermal growth factor (EGF) induces senescence and cyclin-dependent kinase inhibitor 1A (CDKN1A) expression that is related to MITF. We found that MITF could bind TP53 to regulate CDKN1A. Furthermore, the interaction between MITF and TP53 is dependent on AKT activity. We found that AKT phosphorylates MITF at S510. Phosphorylated MITF S510 enhances its affinity to TP53 and promotes CDKN1A expression. Meanwhile, the unphosphorylative MITF promotes TYR expression. The levels of p-MITF-S510 are low in 90% human melanoma samples. Thus the level of p-MITF-S510 could be a possible diagnostic marker for melanoma. Our findings reveal a mechanism for regulating MITF functions in response to EGF stimulation and suggest a possible implementation for preventing the over proliferation of melanoma cells.
MeSH Terms
- Cell Line, Tumor
- Cell Proliferation
- Cellular Senescence
- Cyclin-Dependent Kinase Inhibitor p21
- Gene Expression Regulation, Neoplastic
- Humans
- Inhibitor of Differentiation Proteins
- Melanoma
- Microphthalmia-Associated Transcription Factor
- Phosphorylation
- Proteolysis
- Proto-Oncogene Proteins c-akt
- Tumor Suppressor Protein p53
Keywords
- AKT
- MITF
- Phosphorylation
- Senescence
- TP53
We have previously reported that tyrosol (TYR) promotes lifespan extension in the nematode Caenorhabditis elegans, also inducing a stronger resistance to thermal and oxidative stress in vivo. In this study, we performed a whole-genome DNA microarray in order to narrow down the search for candidate genes or signaling pathways potentially involved in TYR effects on C. elegans longevity. Nematodes were treated with 0 or 250 μM TYR, total RNA was isolated at the adult stage, and derived cDNA probes were hybridized to Affymetrix C. elegans expression arrays. Microarray data analysis was performed, and relative mRNA expression of selected genes was validated using qPCR. Microarray analysis identified 208 differentially expressed genes (206 over-expressed and two under-expressed) when comparing TYR-treated nematodes with vehicle-treated controls. Many of these genes are linked to processes such as regulation of growth, transcription, reproduction, lipid metabolism and body morphogenesis. Moreover, we detected an interesting overlap between the expression pattern elicited by TYR and those induced by other dietary polyphenols known to extend lifespan in C. elegans, such as quercetin and tannic acid. Our results suggest that important cellular mechanisms directly related to longevity are influenced by TYR treatment in C. elegans, supporting our previous notion that this phenol might act on conserved genetic pathways to increase lifespan in a whole organism.
MeSH Terms
- Animals
- Caenorhabditis elegans
- Gene Expression Profiling
- Gene Expression Regulation
- Heat-Shock Proteins
- Lipid Metabolism
- Longevity
- Oligonucleotide Array Sequence Analysis
- Phenylethyl Alcohol
- RNA, Helminth
- RNA, Messenger
- Reproducibility of Results
- Reproduction
- Signal Transduction
- Transcription Factors
Keywords
- Caenorhabditis elegans
- Extra-virgin olive oil
- Longevity
- Microarray
- Tyrosol
Tyrosol (TYR, 2-(4-hydroxyphenyl)ethanol), one of the main phenols in olive oil and olive fruit, significantly strengthens resistance to thermal and oxidative stress in the nematode Caenorhabditis elegans and extends its lifespan. To elucidate the cellular functions regulated by TYR, we have used a proteomic procedure based on 2DE coupled with MS with the aim to identify the proteins differentially expressed in nematodes grown in a medium containing 250 μM TYR. After the comparison of the protein profiles from 250 μM TYR and from control, 28 protein spots were found to be altered in abundance (≥twofold). Analysis by MALDI-TOF/TOF and PMF allowed the unambiguous identification of 17 spots, corresponding to 13 different proteins. These proteins were as follows: vitellogenin-5, vitellogenin-2, bifunctional glyoxylate cycle protein, acyl CoA dehydrogenase-3, alcohol dehydrogenase 1, adenosylhomocysteinase, elongation factor 2, GTP-binding nuclear protein ran-1, HSP-4, protein ENPL-1 isoform b, vacuolar H ATPase 12, vacuolar H ATPase 13, GST 4. Western-blot analysis of yolk protein 170, ras-related nuclear protein, elongation factor 2, and vacuolar H ATPase H subunit supported the proteome evidence.
MeSH Terms
- Animals
- Blotting, Western
- Caenorhabditis elegans
- Caenorhabditis elegans Proteins
- Electrophoresis, Gel, Two-Dimensional
- Longevity
- Mass Spectrometry
- Olea
- Phenols
- Phenylethyl Alcohol
- Proteomics
- Reproducibility of Results
- Stress, Physiological
Keywords
- Animal proteomics
- Caenorhabditis elegans
- Lifespan
- Longevity
- Tyrosol