MDM4 Isoform Expression in Melanoma Supports an Oncogenic Role for MDM4-A
The p53 tumor suppressor integrates upstream signals such as DNA damage and active oncogenes to initiate cell cycle arrest or apoptosis. This response is critical to halting inappropriate growth signals. As such, p53 activity is lost in cancer. In melanoma, however, the p53 gene is intact in a repor...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-01-01
|
| Series: | Journal of Skin Cancer |
| Online Access: | http://dx.doi.org/10.1155/2021/3087579 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832546037041987584 |
|---|---|
| author | Abdullah Alatawi SoonJye Kho Michael P. Markey |
| author_facet | Abdullah Alatawi SoonJye Kho Michael P. Markey |
| author_sort | Abdullah Alatawi |
| collection | DOAJ |
| description | The p53 tumor suppressor integrates upstream signals such as DNA damage and active oncogenes to initiate cell cycle arrest or apoptosis. This response is critical to halting inappropriate growth signals. As such, p53 activity is lost in cancer. In melanoma, however, the p53 gene is intact in a reported 94% of human cases. Rather than direct mutation, p53 is held inactive through interaction with inhibitory proteins. Here, we examine the expression of the two primary inhibitors of p53, MDM2 and MDM4, in genomic databases and biopsy specimens. We find that MDM4 is frequently overexpressed. Moreover, changes in splicing of MDM4 occur frequently and early in melanomagenesis. These changes in splicing must be considered in the design of therapeutic inhibitors of the MDM2/4 proteins for melanoma. |
| format | Article |
| id | doaj-art-08f9c05810854cc3a7519dac463f5aae |
| institution | Kabale University |
| issn | 2090-2905 2090-2913 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Skin Cancer |
| spelling | doaj-art-08f9c05810854cc3a7519dac463f5aae2025-02-03T07:24:01ZengWileyJournal of Skin Cancer2090-29052090-29132021-01-01202110.1155/2021/30875793087579MDM4 Isoform Expression in Melanoma Supports an Oncogenic Role for MDM4-AAbdullah Alatawi0SoonJye Kho1Michael P. Markey2Department of Biochemistry and Molecular Biology, Wright State University, Dayton, OH 45435, USADepartment of Computer Science and Engineering, Wright State University, Dayton, OH 45435, USADepartment of Biochemistry and Molecular Biology, Wright State University, Dayton, OH 45435, USAThe p53 tumor suppressor integrates upstream signals such as DNA damage and active oncogenes to initiate cell cycle arrest or apoptosis. This response is critical to halting inappropriate growth signals. As such, p53 activity is lost in cancer. In melanoma, however, the p53 gene is intact in a reported 94% of human cases. Rather than direct mutation, p53 is held inactive through interaction with inhibitory proteins. Here, we examine the expression of the two primary inhibitors of p53, MDM2 and MDM4, in genomic databases and biopsy specimens. We find that MDM4 is frequently overexpressed. Moreover, changes in splicing of MDM4 occur frequently and early in melanomagenesis. These changes in splicing must be considered in the design of therapeutic inhibitors of the MDM2/4 proteins for melanoma.http://dx.doi.org/10.1155/2021/3087579 |
| spellingShingle | Abdullah Alatawi SoonJye Kho Michael P. Markey MDM4 Isoform Expression in Melanoma Supports an Oncogenic Role for MDM4-A Journal of Skin Cancer |
| title | MDM4 Isoform Expression in Melanoma Supports an Oncogenic Role for MDM4-A |
| title_full | MDM4 Isoform Expression in Melanoma Supports an Oncogenic Role for MDM4-A |
| title_fullStr | MDM4 Isoform Expression in Melanoma Supports an Oncogenic Role for MDM4-A |
| title_full_unstemmed | MDM4 Isoform Expression in Melanoma Supports an Oncogenic Role for MDM4-A |
| title_short | MDM4 Isoform Expression in Melanoma Supports an Oncogenic Role for MDM4-A |
| title_sort | mdm4 isoform expression in melanoma supports an oncogenic role for mdm4 a |
| url | http://dx.doi.org/10.1155/2021/3087579 |
| work_keys_str_mv | AT abdullahalatawi mdm4isoformexpressioninmelanomasupportsanoncogenicroleformdm4a AT soonjyekho mdm4isoformexpressioninmelanomasupportsanoncogenicroleformdm4a AT michaelpmarkey mdm4isoformexpressioninmelanomasupportsanoncogenicroleformdm4a |