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EPLIN-Beta is a novel substrate of ornithine decarboxylase antizyme 1, mediating cellular migration

ABSTRACT: Polyamines promote cellular proliferation, and their levels are controlled by ornithine decarboxylase antizyme 1 (Az1), through the proteasome-mediated, ubiquitin-independent degradation of ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis. Az1-mediated degradation of other substrates such as cyclin D1, DNp73 and Mps1 also regulate cell growth and centrosome amplification. Collectively, the currently known six Az1-substrates are all linked with tumorigenesis. To understand if Az1-mediated protein degradation might play a key role in regulating cellular process associated with tumorigenesis, we employed quantitative proteomics to identify novel Az1 substrates. Here, we describe the identification of LIM domain and Actin-binding protein 1 (LIMA1), also known as epithelial protein lost in neoplasm (EPLIN), as a new target of Az1. Interestingly, between the two isoforms of EPLIN-Alpha and -Beta, only EPLIN-Beta is the substrate of Az1, degraded in an ubiquitination-independent manner. Absence of Az1 led to elevated EPLIN-Beta levels, which caused enhanced cellular migration of Az1-/- cells. Consistently, higher levels of LIMA1 correlated with poorer overall survival of colorectal cancer patients. Taken together, this study identifies EPLIN-Beta as a novel Az1 substrate regulating cellular migration.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Suat Peng Neo

LAB HEAD: Jayantha Gunaratne

PROVIDER: PXD039865 | Pride | 2023-06-08

REPOSITORIES: Pride

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			Action	DRS
	G713_L3L5_proteinGroups.xlsx	Xlsx
	TBP_QE_P6_171118_01_G713L3_A01.raw	Raw
	TBP_QE_P6_171118_02_G713L3_A02.raw	Raw
	TBP_QE_P6_171118_03_G713L3_A03.raw	Raw
	TBP_QE_P6_171118_04_G713L3_A04.raw	Raw

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