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Comparison of the Transcriptional Profiles of Melanocytes from Dark and Light Skinned Individuals under Basal Conditions and Following Ultraviolet-B Irradiation.

López S, Smith-Zubiaga I, García de Galdeano A, Boyano MD, García O, Gardeazábal J, Martinez-Cadenas C, Izagirre N, de la Rúa C, Alonso S - PLoS ONE (2015)

Bottom Line: Our results suggest that an interaction between ribosomal proteins and the P53 signaling pathway may occur in response to UVB in both DM and LM.Furthermore, the culture with KCM+ compared with KCM- had a noticeable effect on LM.This effect includes the activation of various signaling pathways such as the mTOR pathway, involved in the regulation of cell metabolism, growth, proliferation and survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Physical Anthropology and Animal Physiology. University of the Basque Country UPV/EHU, Leioa, Bizkaia, Spain.

ABSTRACT
We analysed the whole-genome transcriptional profile of 6 cell lines of dark melanocytes (DM) and 6 of light melanocytes (LM) at basal conditions and after ultraviolet-B (UVB) radiation at different time points to investigate the mechanisms by which melanocytes protect human skin from the damaging effects of UVB. Further, we assessed the effect of different keratinocyte-conditioned media (KCM+ and KCM-) on melanocytes. Our results suggest that an interaction between ribosomal proteins and the P53 signaling pathway may occur in response to UVB in both DM and LM. We also observed that DM and LM show differentially expressed genes after irradiation, in particular at the first 6h after UVB. These are mainly associated with inflammatory reactions, cell survival or melanoma. Furthermore, the culture with KCM+ compared with KCM- had a noticeable effect on LM. This effect includes the activation of various signaling pathways such as the mTOR pathway, involved in the regulation of cell metabolism, growth, proliferation and survival. Finally, the comparison of the transcriptional profiles between LM and DM under basal conditions, and the application of natural selection tests in human populations allowed us to support the significant evolutionary role of MIF and ATP6V0B in the pigmentary phenotype.

No MeSH data available.


Related in: MedlinePlus

Proposed mechanism for the involvement of ribosomal proteins, MDM2 and p53 signaling pathway in the response to UVB irradiation.
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pone.0134911.g003: Proposed mechanism for the involvement of ribosomal proteins, MDM2 and p53 signaling pathway in the response to UVB irradiation.

Mentions: The role of P53, a tumour suppressor that promotes either cell cycle arrest and DNA repair, apoptosis or senescence [48] in the response to UVB has already been reported [6]. Our results are consistent with the proposed mechanism of P53 pathway regulation by ribosomal proteins [49–51]. Thus, we propose that under stress, there is an upregulation of the ribosomal biogenesis leading to an excess of ribosomal proteins that do not participate in the assembly of ribosomes. Instead, these translocate to the nucleoplasm where they interact with MDM2. Under normal conditions, MDM2 binds to the tumour suppressor P53 inhibiting its transcription. But if ribosomal proteins bind to MDM2, then the inhibition of P53 exerted by MDM2 is suppressed. The upregulation of MDM2 is usually modulated by P53 after the activation of P53-dependent targets, in order to inhibit the activity of P53 and thus restore the normal growth of the cell. However, if the stressing conditions are not completely restablished or DNA damage still exists in the cell, ribosomal proteins could continue interacting with MDM2 to allow to maintain the expression of P53 (Fig 3). Among the ribosomal proteins that can bind to MDM2 are RPL5 [52] and RPL11 [53], both of which were among the upregulated ribosomal genes in this work.


Comparison of the Transcriptional Profiles of Melanocytes from Dark and Light Skinned Individuals under Basal Conditions and Following Ultraviolet-B Irradiation.

López S, Smith-Zubiaga I, García de Galdeano A, Boyano MD, García O, Gardeazábal J, Martinez-Cadenas C, Izagirre N, de la Rúa C, Alonso S - PLoS ONE (2015)

Proposed mechanism for the involvement of ribosomal proteins, MDM2 and p53 signaling pathway in the response to UVB irradiation.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526690&req=5

pone.0134911.g003: Proposed mechanism for the involvement of ribosomal proteins, MDM2 and p53 signaling pathway in the response to UVB irradiation.
Mentions: The role of P53, a tumour suppressor that promotes either cell cycle arrest and DNA repair, apoptosis or senescence [48] in the response to UVB has already been reported [6]. Our results are consistent with the proposed mechanism of P53 pathway regulation by ribosomal proteins [49–51]. Thus, we propose that under stress, there is an upregulation of the ribosomal biogenesis leading to an excess of ribosomal proteins that do not participate in the assembly of ribosomes. Instead, these translocate to the nucleoplasm where they interact with MDM2. Under normal conditions, MDM2 binds to the tumour suppressor P53 inhibiting its transcription. But if ribosomal proteins bind to MDM2, then the inhibition of P53 exerted by MDM2 is suppressed. The upregulation of MDM2 is usually modulated by P53 after the activation of P53-dependent targets, in order to inhibit the activity of P53 and thus restore the normal growth of the cell. However, if the stressing conditions are not completely restablished or DNA damage still exists in the cell, ribosomal proteins could continue interacting with MDM2 to allow to maintain the expression of P53 (Fig 3). Among the ribosomal proteins that can bind to MDM2 are RPL5 [52] and RPL11 [53], both of which were among the upregulated ribosomal genes in this work.

Bottom Line: Our results suggest that an interaction between ribosomal proteins and the P53 signaling pathway may occur in response to UVB in both DM and LM.Furthermore, the culture with KCM+ compared with KCM- had a noticeable effect on LM.This effect includes the activation of various signaling pathways such as the mTOR pathway, involved in the regulation of cell metabolism, growth, proliferation and survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Physical Anthropology and Animal Physiology. University of the Basque Country UPV/EHU, Leioa, Bizkaia, Spain.

ABSTRACT
We analysed the whole-genome transcriptional profile of 6 cell lines of dark melanocytes (DM) and 6 of light melanocytes (LM) at basal conditions and after ultraviolet-B (UVB) radiation at different time points to investigate the mechanisms by which melanocytes protect human skin from the damaging effects of UVB. Further, we assessed the effect of different keratinocyte-conditioned media (KCM+ and KCM-) on melanocytes. Our results suggest that an interaction between ribosomal proteins and the P53 signaling pathway may occur in response to UVB in both DM and LM. We also observed that DM and LM show differentially expressed genes after irradiation, in particular at the first 6h after UVB. These are mainly associated with inflammatory reactions, cell survival or melanoma. Furthermore, the culture with KCM+ compared with KCM- had a noticeable effect on LM. This effect includes the activation of various signaling pathways such as the mTOR pathway, involved in the regulation of cell metabolism, growth, proliferation and survival. Finally, the comparison of the transcriptional profiles between LM and DM under basal conditions, and the application of natural selection tests in human populations allowed us to support the significant evolutionary role of MIF and ATP6V0B in the pigmentary phenotype.

No MeSH data available.


Related in: MedlinePlus