Structure vs. Function of TRIB1—Myeloid Neoplasms and Beyond
The Tribbles family of proteins—comprising TRIB1, TRIB2, TRIB3 and more distantly related STK40—play important, but distinct, roles in differentiation, development and oncogenesis. Of the four Tribbles proteins, TRIB1 has been most well characterised structurally and plays roles in diverse cancer ty...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-06-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/12/3060 |
| _version_ | 1797529574201884672 |
|---|---|
| author | Hamish D McMillan Karen Keeshan Anita K Dunbier Peter D Mace |
| author_facet | Hamish D McMillan Karen Keeshan Anita K Dunbier Peter D Mace |
| author_sort | Hamish D McMillan |
| collection | DOAJ |
| description | The Tribbles family of proteins—comprising TRIB1, TRIB2, TRIB3 and more distantly related STK40—play important, but distinct, roles in differentiation, development and oncogenesis. Of the four Tribbles proteins, TRIB1 has been most well characterised structurally and plays roles in diverse cancer types. The most well-understood role of TRIB1 is in acute myeloid leukaemia, where it can regulate C/EBP transcription factors and kinase pathways. Structure–function studies have uncovered conformational switching of TRIB1 from an inactive to an active state when it binds to C/EBPα. This conformational switching is centred on the active site of TRIB1, which appears to be accessible to small-molecule inhibitors in spite of its inability to bind ATP. Beyond myeloid neoplasms, TRIB1 plays diverse roles in signalling pathways with well-established roles in tumour progression. Thus, TRIB1 can affect both development and chemoresistance in leukaemia; glioma; and breast, lung and prostate cancers. The pervasive roles of TRIB1 and other Tribbles proteins across breast, prostate, lung and other cancer types, combined with small-molecule susceptibility shown by mechanistic studies, suggests an exciting potential for Tribbles as direct targets of small molecules or biomarkers to predict treatment response. |
| first_indexed | 2024-03-10T10:15:39Z |
| format | Article |
| id | doaj.art-7670f72299784684b659705a0738b9f6 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T10:15:39Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-7670f72299784684b659705a0738b9f62023-11-22T00:51:09ZengMDPI AGCancers2072-66942021-06-011312306010.3390/cancers13123060Structure vs. Function of TRIB1—Myeloid Neoplasms and BeyondHamish D McMillan0Karen Keeshan1Anita K Dunbier2Peter D Mace3Biochemistry Department, School of Biomedical Sciences, University of Otago, P.O. Box 56, Dunedin 9054, New ZealandPaul O’Gorman Leukaemia Research Centre, Institute of Cancer Sciences, University of Glasgow, Scotland G12 0YN, UKBiochemistry Department, School of Biomedical Sciences, University of Otago, P.O. Box 56, Dunedin 9054, New ZealandBiochemistry Department, School of Biomedical Sciences, University of Otago, P.O. Box 56, Dunedin 9054, New ZealandThe Tribbles family of proteins—comprising TRIB1, TRIB2, TRIB3 and more distantly related STK40—play important, but distinct, roles in differentiation, development and oncogenesis. Of the four Tribbles proteins, TRIB1 has been most well characterised structurally and plays roles in diverse cancer types. The most well-understood role of TRIB1 is in acute myeloid leukaemia, where it can regulate C/EBP transcription factors and kinase pathways. Structure–function studies have uncovered conformational switching of TRIB1 from an inactive to an active state when it binds to C/EBPα. This conformational switching is centred on the active site of TRIB1, which appears to be accessible to small-molecule inhibitors in spite of its inability to bind ATP. Beyond myeloid neoplasms, TRIB1 plays diverse roles in signalling pathways with well-established roles in tumour progression. Thus, TRIB1 can affect both development and chemoresistance in leukaemia; glioma; and breast, lung and prostate cancers. The pervasive roles of TRIB1 and other Tribbles proteins across breast, prostate, lung and other cancer types, combined with small-molecule susceptibility shown by mechanistic studies, suggests an exciting potential for Tribbles as direct targets of small molecules or biomarkers to predict treatment response.https://www.mdpi.com/2072-6694/13/12/3060TribblesTRIB1TRIB2leukaemiabreast cancerprostate cancer |
| spellingShingle | Hamish D McMillan Karen Keeshan Anita K Dunbier Peter D Mace Structure vs. Function of TRIB1—Myeloid Neoplasms and Beyond Cancers Tribbles TRIB1 TRIB2 leukaemia breast cancer prostate cancer |
| title | Structure vs. Function of TRIB1—Myeloid Neoplasms and Beyond |
| title_full | Structure vs. Function of TRIB1—Myeloid Neoplasms and Beyond |
| title_fullStr | Structure vs. Function of TRIB1—Myeloid Neoplasms and Beyond |
| title_full_unstemmed | Structure vs. Function of TRIB1—Myeloid Neoplasms and Beyond |
| title_short | Structure vs. Function of TRIB1—Myeloid Neoplasms and Beyond |
| title_sort | structure vs function of trib1 myeloid neoplasms and beyond |
| topic | Tribbles TRIB1 TRIB2 leukaemia breast cancer prostate cancer |
| url | https://www.mdpi.com/2072-6694/13/12/3060 |
| work_keys_str_mv | AT hamishdmcmillan structurevsfunctionoftrib1myeloidneoplasmsandbeyond AT karenkeeshan structurevsfunctionoftrib1myeloidneoplasmsandbeyond AT anitakdunbier structurevsfunctionoftrib1myeloidneoplasmsandbeyond AT peterdmace structurevsfunctionoftrib1myeloidneoplasmsandbeyond |