Biology subjects

Neo, S. P.

Publications and source records attributed to Neo, S. P..

3 recordsLinked to original sources

bioRxiv2022

Epithelial protein lost in neoplasm (EPLIN)-beta is a novel substrate of ornithine decarboxylase antizyme 1, mediating cellular migration

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 cellular migration and centrosome amplification, and 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. In this report, 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 ( and {beta}), only EPLIN-{beta} is the substrate of Az1, degraded in a proteasome-dependent and ubiquitination-independent manner. Absence of Az1 led to elevated EPLIN-{beta} levels, which is causal to enhanced cellular migration of Az1-/- cells. Consistently, higher levels of LIMA1 expression correlated with poorer overall survival of colorectal cancer patients. Taken together, this study identifies EPLIN-{beta} as a novel Az1 substrate that regulates cellular migration.

cancer biology↗

bioRxiv2022

A potential interacting network identified by quantitative proteomics for the sole adenylyl cyclase Cyr1 of Candida albicans

Cyr1, the sole adenylyl cyclase of the fungal pathogen Candida albicans, is a central component of the cAMP/PKA signaling pathway that controls the yeast-to-hyphal morphogenesis. Cyr1 functions as a multivalent senor and integrator of various external and internal signals. To better understand how these signals are relayed to Cyr1 and how Cyr1 activity is regulated, we sought to identify global interacting partners of Cyr1 using stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics. From the proteins co-immunoprecipitated with Myc-tagged Cyr1, 38 were assigned as authentic Cyr1-interacting partners, including two previously characterized Cyr1-binding proteins, Cap1 and Act1. Many of the identified proteins remain uncharacterized, but some can be classified into several functional groups, such as actin regulatory proteins, cell wall components, and mitochondrial proteins. We used biochemical and genetic methods to further characterize the interaction of Cyr1 with Mp65, a cell surface mannoprotein previously reported to have a role in cell wall integrity and possess several virulence-related traits. Taken together, our comprehensive analysis of the Cyr1-interacting proteins provides important information for establishing the Cyr1 interactome and uncovers a potential role for cell wall proteins in Cyr1-mediated cAMP signaling.

microbiology↗

bioRxiv2021

Tensin3 interaction with talin drives formationof fibronectin-associated fibrillar adhesions

The formation of healthy tissue involves continuous remodelling of the extracellular matrix (ECM). Whilst it is known that this requires integrin-associated cell-ECM adhesion sites (CMAs) and actomyosin-mediated forces, the underlying mechanisms remain unclear. Here we examine how tensin3 contributes to formation of fibrillar adhesions (FBs) and fibronectin fibrillo-genesis. Using BioID mass spectrometry and a mitochondrial targeting assay, we establish that tensin3 associates with the mechanosensors talin and vinculin. We show that the talin R11 rod domain binds directly to a helical motif within the central intrinsically disordered region (IDR) of tensin3, whilst vinculin binds indirectly to tensin3 via talin. Using CRISPR knock-out cells in combination with defined tensin3 mutations, we show (i) that tensin3 is critical for formation of 5{beta}1-integrin FBs and for fibronectin fibrillogenesis, and (ii) the talin/tensin3 interaction drives this process, with vinculin acting to potentiate it.

cell biology↗