Biology subjects

Flores, E.

Publications and source records attributed to Flores, E..

22 records · Page 2Linked to original sources

bioRxiv2021

Hidden structure in disordered proteins is adaptive to intracellular changes

Intrinsically disordered proteins and protein regions (IDPs) are essential to cellular function in all proteomes. Unlike folded proteins, IDPs exist in an ensemble of rapidly interchanging conformations. IDP sequences encode interactions that create structural biases within the ensemble. Such structural biases determine the three-dimensional shape of IDP ensembles and can affect their activity. However, the plasticity and sensitivity of IDP ensembles means structural biases, often measured in vitro, may differ in the dynamic and heterogeneous intracellular environment. Here we reveal that structural biases found in vitro in well-studied IDPs persist inside human-derived cells. We further show that a subset of IDPs are able to sense changes in cellular physical-chemical composition and modulate their ensemble in response. We propose that IDP ensembles can evolve to sense and respond to intracellular physicochemical changes, or to resist them. This property can be leveraged for biological function, be the underlying cause of IDP-driven pathology, or be leveraged for the design of disorder-based biosensors and actuators.

biophysics↗

bioRxiv2021

CmP signaling network unveils novel biomarkers for triple negative breast cancer in African American women

Breast cancer is the most commonly diagnosed cancer worldwide and remains the second leading cause of cancer death. While breast cancer mortality has steadily declined over the past decades through medical advances, an alarming disparity in breast cancer mortality has emerged between African American women (AAW) and Caucasian American women (CAW); and new evidence suggests more aggressive behavior of triple-negative breast cancer (TNBC) in AAW may contribute to racial differences in tumor biology and mortality. Progesterone (PRG) is capable of exerting its cellular effects through either its classic, non-classic or combined responses through binding to either classic nuclear PRG receptors (nPRs) or non-classic membrane PRG receptors (mPRs), warranting both pathways an equally important status in PRG-mediated signaling. In our previous report, we demonstrated that the CCM signaling complex (CSC) consisting of CCM1, CCM2, and CCM3 proteins can couple both nPRs and mPRs signaling cascades to form a CSC-mPRs-PRG-nPRs (CmPn) signaling network in nPR positive(+) breast cancer cells. In this report, we furthered our research by establishing the CSC-mPRs-PRG (CmP) signaling network in nPR(-) breast cancer cells, demonstrating that a common core mechanism exists, regardless of nPR(+/-) cell type. This is the first report stating that inducible expression patterns exist between CCMs and major mPRs in TNBC cells. Furthermore, we firstly show mPRs in TNBC cells are localized in the nucleus and participate in nucleocytoplasmic shuttling in a coordinately synchronized fashion with CCM proteins under steroid actions, following the same cellular distribution as other well-defined steroid hormone receptors. Finally, for the first time, we deconvoluted the CmP signalosome by using multi-omics approaches, which helped us understand key factors within the CmP network, and identify 21 specific biomarkers with potential clinical applications associated with AAW-TNBC tumorigenesis. These novel biomarkers could have immediate clinical implications to dramatically improve health disparities among AAW-TNBCs.

cancer biology↗

bioRxiv2020

Hydration-dependent phase separation of a prion-like protein regulates seed germination during water stress.

Many organisms evolved strategies to survive and thrive under extreme desiccation. Plant seeds protect dehydrated embryos from a variety of stressors and can even lay dormant for millennia. While hydration is the key trigger that reactivates metabolism and kick-starts germination, the exact mechanism by which the embryo senses water remains unresolved. We identified an uncharacterized Arabidopsis thaliana prion-like protein we named FLOE1, which phase separates upon hydration and allows the embryo to sense water stress. We demonstrate that the biophysical states of FLOE1 condensates modulate its biological function in vivo in suppressing seed germination under unfavorable environments. We also find intragenic, intraspecific, and interspecific natural variations in phase separation propensity of FLOE1 homologs. These findings demonstrate a physiological role of phase separation in a multicellular organism and have direct implications for plant ecology and agriculture, especially the design of drought resistant crops, in the face of climate change.

cell biology↗

bioRxiv2017

Targeting the Untargetable: Predicting Pramlintide Resistance Using a Neural Network Based Cellular Automata

De novo resistance is a major issue for the use of targeted anticancer drugs in the clinic. By integrating experimental data we have created a hybrid neural network/agent-based model to simulate the evolution and spread of resistance to the drug Pramlintide in cutaneous squamous cell carcinoma. Our model can eventually be used to predict patient responses to the drug and thus enable clinicians to make decisions regarding personalized, precision treatment regimes for patients.

cancer biology↗