Graduation Date

Fall 12-18-2020

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Biochemistry & Molecular Biology

First Advisor

Dr. Vimla Band

Abstract

The mammalian orthologue of the evolutionarily conserved Ecdysoneless (ECD) protein is required for embryogenesis, cell cycle progression and mitigation of ER stress. However, the molecular mechanisms of ECD function in mammalian cells remain unclear. Here, using mass spectrometry analysis of the mammalian ECD interactome, we identified several components of the mRNA export complexes as binding partners of ECD and then characterized the functional interaction of ECD with key mRNA export-related DEAD BOX protein helicase DDX39A and its associated partners. FISH analysis of Poly-A-tailed mRNAs revealed that ECD depletion/deletion blocks the mRNA export from the nucleus to the cytoplasm. We have previously shown that ECD is overexpressed in ErbB2+ breast cancers. ECD depletion in ErbB2+ breast cancer cells led to a decrease in ErbB2 mRNA level due to a block in its nuclear export and was associated with impairment of oncogenic traits. Given the essential role of ECD in mouse embryogenesis and ECD overexpression in multiple human cancers, our findings that ECD is required for efficient mRNA export provides a novel mechanistic insight into physiological and pathological function of ECD.

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