Developing Targeted Therapies That Exploit Aberrant Histone Ubiquitination in Cancer
Histone ubiquitination is a critical epigenetic mechanism regulating DNA-driven processes such as gene transcription and DNA damage repair. Importantly, the cellular machinery regulating histone ubiquitination is frequently altered in cancers. Moreover, aberrant histone ubiquitination can drive onco...
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/2/165 |
| _version_ | 1827852078137999360 |
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| author | Lucile M-P Jeusset Kirk J McManus |
| author_facet | Lucile M-P Jeusset Kirk J McManus |
| author_sort | Lucile M-P Jeusset |
| collection | DOAJ |
| description | Histone ubiquitination is a critical epigenetic mechanism regulating DNA-driven processes such as gene transcription and DNA damage repair. Importantly, the cellular machinery regulating histone ubiquitination is frequently altered in cancers. Moreover, aberrant histone ubiquitination can drive oncogenesis by altering the expression of tumor suppressors and oncogenes, misregulating cellular differentiation and promoting cancer cell proliferation. Thus, targeting aberrant histone ubiquitination may be a viable strategy to reprogram transcription in cancer cells, in order to halt cellular proliferation and induce cell death, which is the basis for the ongoing development of therapies targeting histone ubiquitination. In this review, we present the normal functions of histone H2A and H2B ubiquitination and describe the role aberrant histone ubiquitination has in oncogenesis. We also describe the key benefits and challenges associated with current histone ubiquitination targeting strategies. As these strategies are predicted to have off-target effects, we discuss additional efforts aimed at developing synthetic lethal strategies and epigenome editing tools, which may prove pivotal in achieving effective and selective therapies targeting histone ubiquitination, and ultimately improving the lives and outcomes of those living with cancer. |
| first_indexed | 2024-03-12T10:44:54Z |
| format | Article |
| id | doaj.art-b5c7671e97b14e579013e1789ae8f5f4 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T10:44:54Z |
| publishDate | 2019-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b5c7671e97b14e579013e1789ae8f5f42023-09-02T07:44:05ZengMDPI AGCells2073-44092019-02-018216510.3390/cells8020165cells8020165Developing Targeted Therapies That Exploit Aberrant Histone Ubiquitination in CancerLucile M-P Jeusset0Kirk J McManus1Department of Biochemistry & Medical Genetics, University of Manitoba, Winnipeg, MB R3E 0J9, CanadaDepartment of Biochemistry & Medical Genetics, University of Manitoba, Winnipeg, MB R3E 0J9, CanadaHistone ubiquitination is a critical epigenetic mechanism regulating DNA-driven processes such as gene transcription and DNA damage repair. Importantly, the cellular machinery regulating histone ubiquitination is frequently altered in cancers. Moreover, aberrant histone ubiquitination can drive oncogenesis by altering the expression of tumor suppressors and oncogenes, misregulating cellular differentiation and promoting cancer cell proliferation. Thus, targeting aberrant histone ubiquitination may be a viable strategy to reprogram transcription in cancer cells, in order to halt cellular proliferation and induce cell death, which is the basis for the ongoing development of therapies targeting histone ubiquitination. In this review, we present the normal functions of histone H2A and H2B ubiquitination and describe the role aberrant histone ubiquitination has in oncogenesis. We also describe the key benefits and challenges associated with current histone ubiquitination targeting strategies. As these strategies are predicted to have off-target effects, we discuss additional efforts aimed at developing synthetic lethal strategies and epigenome editing tools, which may prove pivotal in achieving effective and selective therapies targeting histone ubiquitination, and ultimately improving the lives and outcomes of those living with cancer.https://www.mdpi.com/2073-4409/8/2/165histoneH2AH2BubiquitinationdeubiquitinationE3 ubiquitin ligasecancerepigenetic therapysynthetic lethalityepigenome editing |
| spellingShingle | Lucile M-P Jeusset Kirk J McManus Developing Targeted Therapies That Exploit Aberrant Histone Ubiquitination in Cancer Cells histone H2A H2B ubiquitination deubiquitination E3 ubiquitin ligase cancer epigenetic therapy synthetic lethality epigenome editing |
| title | Developing Targeted Therapies That Exploit Aberrant Histone Ubiquitination in Cancer |
| title_full | Developing Targeted Therapies That Exploit Aberrant Histone Ubiquitination in Cancer |
| title_fullStr | Developing Targeted Therapies That Exploit Aberrant Histone Ubiquitination in Cancer |
| title_full_unstemmed | Developing Targeted Therapies That Exploit Aberrant Histone Ubiquitination in Cancer |
| title_short | Developing Targeted Therapies That Exploit Aberrant Histone Ubiquitination in Cancer |
| title_sort | developing targeted therapies that exploit aberrant histone ubiquitination in cancer |
| topic | histone H2A H2B ubiquitination deubiquitination E3 ubiquitin ligase cancer epigenetic therapy synthetic lethality epigenome editing |
| url | https://www.mdpi.com/2073-4409/8/2/165 |
| work_keys_str_mv | AT lucilempjeusset developingtargetedtherapiesthatexploitaberranthistoneubiquitinationincancer AT kirkjmcmanus developingtargetedtherapiesthatexploitaberranthistoneubiquitinationincancer |