Molecular and cellular studies on the 2-oxoglutarate-dependent oxygenase MINA53

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Hendrix, Eline ORCID: https://orcid.org/0000-0002-1188-4484 (2021). Molecular and cellular studies on the 2-oxoglutarate-dependent oxygenase MINA53. University of Birmingham. Ph.D.

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Abstract

Human 2-oxoglutarate (2OG) and iron-dependent oxygenases catalyse an emerging post-translational modification, hydroxylation, on a range of substrates including DNA, RNA and protein. Despite the well-recognised roles of 2OG oxygenases in oxygen sensing and epigenetic regulation of transcription, much work remains to be done to elucidate the roles of the less well-characterised family members in physiology and disease. Myc-induced nuclear antigen (MINA) is a 2OG oxygenase that catalyses histidyl hydroxylation of the large ribosomal subunit protein RPL27A. The paradoxical role of MINA in cancer, however, suggests the potential existence of additional substrates or functions. Here, we identify and explore a novel role of MINA in epithelial morphogenesis. We begin by characterising the physiological and pathological cues that contribute to the nucleolar retention and release of MINA. We then identify and characterise a novel activity-dependent and extra-nucleolar interaction between MINA and a membrane-associated guanylate kinase, membrane palmitoylated protein 6 (MPP6). Subsequent studies explored the role of MINA localisation, activity and MPP6 in epithelial morphogenesis. Overall, our findings suggest that extra-nucleolar MINA functions as a tumour suppressor, possibly through its interaction with MPP6. Moreover, the work presented in this thesis suggests a novel mechanism by which the tumour suppressor function of MINA may be broadly inactivated in cancer.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
Supervisor(s):
Supervisor(s)EmailORCID
Coleman, MathewUNSPECIFIEDUNSPECIFIED
Sarkar, SovanUNSPECIFIEDUNSPECIFIED
Licence: All rights reserved
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: Institute of Cancer and Genomic Sciences
Funders: Biotechnology and Biological Sciences Research Council
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
URI: http://etheses.bham.ac.uk/id/eprint/11863

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