Biology subjects

Shao, Q.

Publications and source records attributed to Shao, Q..

At least 19 recordsLinked to original sources

bioRxiv2026

Benchmark Averages Hide the Failures That Matter: Quantizing ESM-2 for Protein Variant-Effect Prediction

We benchmark six numerical precision configurations for ESM-2 protein language models across throughput, memory footprint and predictive accuracy, on two workloads with sharply different characteristics: bulk embedding extraction and deep mutational scanning (DMS) variant-effect scoring. Accuracy is evaluated on the complete ProteinGym substitution benchmark -- 201 assays, 2.41M variants -- at three model scales spanning 650M to 15B parameters, with a paired bootstrap clustered on protein. Three findings follow, and each contradicts a common practice. First, benchmark averages conceal the failure that decides deployability: no configuration shifts mean correlation by more than 0.007 at any scale, yet INT8 dynamic quantization -- indistinguishable from fp32 on that mean at 3B (p = 0.34) -- takes a single assay from{rho} = 0.591 to 0.223. Selection must be made on worst-case, not mean, behaviour. Second, fidelity measured against fp32 bounds risk but cannot rank quality: over 3015 assay/configuration pairs it predicts the magnitude of ground-truth change (r = 0.56-0.81) but not its direction, and the INT4 effect differs significantly between 650M and 3B (+0.0101, p = 0.0007) with no monotone trend to extrapolate. Third, quantizing a large model is dominated by using a small one: of eighteen scale/configuration combinations only three are Pareto-optimal over accuracy, memory and speed, and all three are 650M. The one catastrophic failure we observe is a defect of default symmetric activation scaling, not of W8A8 itself: asymmetric activation quantization, a one-line change needing no calibration, removes every damaged assay. We also give a label-free screen for at-risk targets, and report four measurement artifacts encountered during this study, three of which inverted the result they were meant to measure.

bioinformatics↗

bioRxiv2026

Critical reassessment of lipophilic dye labeling reveals negligible incorporation into small extracellular vesicles derived form serum-free cultured cells

Lipophilic dyes are widely used to track extracellular vesicles (EVs), yet their labeling efficiency toward bona fide small EVs (sEVs) remains poorly defined. Using a serum-free HEK293F system that produces endogenously fluorescent protein-tagged sEVs (sEVs-FPT) as an unambiguous reference while minimizing interference from dye-binding non-vesicular particles, we reassessed this efficiency with two orthogonal methods: nanoflow cytometry and fluorescence microscopy. PKH26, PKH67, and DiD labeled less than 0.5% of sEVs-FPT, regardless of vesicle heterogeneity. In vivo, dye-derived signals were far less abundant than tag-derived signals and failed to colocalize with them. Mechanistic evidence indicates that this failure stems from the inability of sEVs, as acellular structures, to actively internalize dye aggregates. These findings reveal a fundamental limitation of lipophilic dye-based EV tracking and underscore the need for orthogonally validated labeling strategies. One Sentence SummaryLipophilic dyes fail to label bona fide small extracellular vesicles, calling dye-based vesicle tracking into question.

bioengineering↗

bioRxiv2026

DPLM: Dynamics-aware Protein Language Model via contrastive learning between sequence and molecular dynamics simulation trajectory

Protein dynamics play a critical role in protein function, yet such important information is missing in many protein language models (PLM). We introduce DPLM, a dynamics-aware protein language model that aligns sequence embeddings with molecular dynamics (MD) trajectory embeddings via contrastive learning. Using MD features encoded by a pretrained video model, DPLM learns sequence representations that correlate with residue-level flexibility and improve protein-level functional clustering compared to static sequence- and structure-based PLMs. Without task-specific training, DPLM outperforms ESM-based representations in zero-shot mutation-effect prediction on multiple deep mutational scanning datasets. When adapted with lightweight task-specific heads, DPLM further achieves top-tier performance on protein stability prediction and intrinsic disorder region identification, demon-strating that contrastive alignment with MD trajectories enables PLMs to capture biologically meaningful dynamic properties.

bioinformatics↗

bioRxiv2025

Ser129 Phosphorylation Paradox: Non-phosphorylated α-Synuclein Drives Parkinson' s Disease-like Pathogenesis in Vivo

Accumulation of phosphorylated -synuclein at serine 129 is a hallmark of Parkinsons disease (PD), but its pathogenic role remains controversial. We conducted longitudinal studies using non-phosphorylatable S129A and phosphomimetic S129D -synuclein global knock-in mice. Unexpectedly, the S129A mice--rather than S129D mice--developed reproducible olfactory, motor, and cognitive deficits, dopaminergic dysfunction and neurodegeneration, -synuclein insolubility, and Lewy-like inclusions by 3 to 9 months, with progressive worsening up to 12 months of age. Spatial transcriptomics and electron microscopy revealed mitochondrial, synaptic, and protein ubiquitination abnormalities in the substantia nigra of S129A -synuclein mice. Viral vector-mediated nigral overexpression of S129D--synuclein or systemic administration of an anti--synuclein-aggregation drug partially alleviated the early neurological phenotypes of S129A mice. These results implicate non-phosphorylatable -synuclein as a direct pathogenic driver for PD.

neuroscience↗

bioRxiv2025

Discovery of Non-Degradative Covalent Molecular Glues for Transcriptional Reprogramming

Transcriptional reprogramming through induced proximity has emerged as a powerful strategy for modulating the expression of oncogenic and tumor-suppressive genes. Inspired by transcriptional reprogramming approaches such as transcriptional/epigenetic chemical inducers of proximity (TCIPs) that link BCL6 inhibitors to transcriptional regulators, we sought to develop covalent ligands that rewire BCL6 proximity to selectively suppress MYC transcriptional output while derepressing BCL6 target loci. Through a chemistry-driven and chemoproteomics-enabled design strategy, we generated a panel of BCL6-based electrophile-bearing hybrid ligands and identified a nondegradative molecular glue, ZD-1-186, that potently suppresses MYC and robustly induces CDKN1A (p21) in diffuse large B-cell lymphoma cells. ZD-1-186 downregulates MYC more effectively than BCL6 inhibitors or degraders, while strongly derepressing canonical BCL6 targets, including p21. Through BCL6 pulldown proteomics, ZD-1-186 induced a selective recruitment of the noncanonical BAF complex subunit BRD9 to BCL6 and covalently modified BRD9 at C288. Pharmacologic inhibition or genetic knockdown of BRD9 attenuated ZD-1-186-mediated MYC suppression and blunted p21 induction. Transcriptomic profiling of ZD-1-186 showed simultaneous derepression of BCL6-repressive loci and suppression of MYC transcriptional programs. These findings demonstrated that ZD-1-186 acted as a transcriptional rewiring glue, recruiting BRD9 to BCL6-repressive loci to activate tumor-suppressive transcription, while also potentially redirecting BCL6 to BRD9-bound oncogenic loci. Overall, our work provides a blueprint for the rational discovery and design of electrophile-enabled, nondegradative molecular glues for targeted transcriptional rewiring.

biochemistry↗

bioRxiv2025

ProtLoc-GRPO: Cell line-specific subcellular localization prediction using a graph-based model and reinforcement learning

Subcellular localization prediction is crucial for understanding protein functions and cellular processes. Subcellular localization is dependent on tissue and cell lines derived from different cell types. Predicting cell line-specific subcellular localization using the information of protein-protein interactions (PPIs) offers deeper insights into dynamic cellular organization and molecular mechanisms. However, many existing PPI networks contain systematic errors that limit prediction accuracy. In this study, we propose a reinforcement learning approach, ProtLoc-GRPO, to enhance subcellular localization prediction by optimizing the structure of the underlying PPI network. ProtLoc-GRPO learns to rank and retain the most informative PPI edges to maximize the macro-F1 score for cell line-specific subcellular localization. Our approach yields a 7% improvement in macro-F1 score over the baseline. We further evaluate its robustness across various edge pruning rates and benchmark it against conventional pruning strategies. Results show that our proposed method consistently outperforms existing approaches. To our knowledge, this work represents the first study to predict cell line-specific protein subcellular localization and the first application of the Group Relative Policy Optimization (GRPO) framework to a graph-based model for bioinformatics tasks.

bioinformatics↗

bioRxiv2025

PLK1-mediated phosphorylation of PHGDH reprograms serine metabolism in advanced prostate cancer

Metabolic reprogramming is a hallmark of cancer, enabling tumor cells to meet their increased biosynthetic and energetic demands. While cells possess the capacity for de novo serine biosynthesis, most transformed cancer cells heavily depend on exogenous serine uptake to sustain their growth, yet the regulatory mechanisms driving this metabolic dependency remain poorly understood. Here, we uncover a novel mechanism by which Polo-like kinase 1 (PLK1), often overexpressed in prostate cancer, orchestrates a metabolic shift in serine and lipid metabolism through the phosphorylation of phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme of the serine synthesis pathway (SSP). We demonstrate that PLK1 phosphorylates PHGDH at three specific sites (S512, S513, S517), leading to a marked reduction in its protein level and enzymatic activity. This downregulation of SSP forces cancer cells to increase their reliance on exogenous serine uptake via the ASCT2 transporter, which, in turn, fuels the biosynthesis of lipids, including sphingolipids essential for tumor growth and survival. Targeting the SSP, serine uptake, or downstream lipid biosynthetic pathways may offer promising therapeutic avenues in PLK1-high advanced cancers.

cancer biology↗

bioRxiv2025

Enhancing Structure-aware Protein Language Models with Efficient Fine-tuning for Various Protein Prediction Tasks

Proteins are crucial in a wide range of biological and engineering processes. Large protein language models (PLMs) can significantly advance our understanding and engineering of proteins. However, the effectiveness of PLMs in prediction and design is largely based on the representations derived from protein sequences. Without incorporating the three-dimensional structures of proteins, PLMs would overlook crucial aspects of how proteins interact with other molecules, thereby limiting their predictive accuracy. To address this issue, we present S-PLM, a 3D structure-aware PLM that employs multi-view contrastive learning to align protein sequences with their 3D structures in a unified latent space. Previously, we utilized a contact map-based approach to encode structural information, applying the Swin-Transformer to contact maps derived from AlphaFold-predicted protein structures. This work introduces a new approach that leverages a Geometric Vector Perceptron (GVP) model to process 3D coordinates and obtain structural embeddings. We focus on the application of structure-aware models for protein-related tasks by utilizing efficient fine-tuning methods to achieve optimal performance without significant computational costs. Our results show that S-PLM outperforms sequence-only PLMs across all protein clustering and classification tasks, achieving performance on par with state-of-the-art methods that require both sequence and structure inputs. S-PLM and its tuning tools are available at https://github.com/duolinwang/S-PLM/.

bioinformatics↗

bioRxiv2025

HIF-1α/STOML2 mediated PINK1-dependent mitophagy activation against hypoxia-induced neuronal injury

Hypoxia contributes to brain disorders by causing neuronal injury. However, in the early stage of stress, neurons initiate a series of compensatory pathways to resist cell damage, but the underlying mechanisms have not been fully elucidated. In this study, we found that hypoxia transiently activates PTEN-induced kinase 1 (PINK1)-dependent mitophagy in the early stage before cell damage and neurological dysfunction. PINK1 overexpression protects neurons and it knockdown exacerbates neuronal damage, highlighting the key role of PINK1-dependent mitophagy in hypoxic adaptation. Mechanistically, hypoxia promotes HIF-1 nuclear translocation, inducing transcription of stomatin like 2 (STOML2). STOML2 relocates to the mitochondrial membrane, aiding phosphoglycerate mutase 5 (PGAM5) cleavage, which triggers PINK1-dependent mitophagy. Silencing HIF-1, STOML2, or PGAM5 inhibits PINK1-dependent mitophagy and worsens neurological function under hypoxia. Notably, intermittent hypoxia, a hypoxic conditioning strategy for improving hypoxic tolerance, enhances PINK1-dependent mitophagy by activating HIF-1/STOML2 axis, and protects neurons against hypoxia. In conclusion, our study reveals a new "self-protection" mechanism of neurons against hypoxic stress and discovers that intermittent hypoxia is a potential therapeutic strategy against hypoxia-induced injury.

neuroscience↗

bioRxiv2025

Small non-coding RNAs encapsulating mammalian cells fuel innate immunity

Cell surface RNAs, notably glycoRNAs, have been reported, yet the exact surface RNA compositions in different cell types remain unclear. Here, we introduce a comprehensive suite of methodologies for imaging, profiling, quantifying, and exploring the biological functions of specific surface RNAs. Utilizing these techniques, we have identified diverse non-coding RNAs present on mammalian cell surfaces. We confirm the membrane anchorage and quantify the abundance of several representative RNAs on human primary cells. Notably, we discover a significant prevalence of Y RNAs on the surfaces of human monocytes and B cells. We find that these Y RNAs on human monocyte surfaces enrich extracellular histones, regulating interleukin-6 (IL-6) gene expression and subsequent protein secretion upon histone stimulation via NF-{kappa}B and AP-1 activation. Our study not only presents effective approaches for investigating surface RNAs, but also uncovers a previously unrecognized immune activation pathway mediated by surface Y RNAs on monocytes. In briefA comprehensive profiling of surface RNAs across diverse mammalian blood cell types unveil abundant Y RNAs on the surface of human monocytes. Subsequent investigations uncover functional roles of surface Y RNAs on monocytes as "immune sentinel" to enrich extracellular histones, revealing a previously unknown pathway of innate immune activation. HighlightsNovel methodologies for cell surface RNA mapping, validation and functional interrogation. Sequencing of surface RNAs across various mammalian blood cell types offers detailed maps of surface RNAs. Abundant Y RNAs localize on human monocyte surfaces and capture extracellular histones released by adjacent ruptured cells. Surface Y RNAs enrich extracellular histones to facilitate transcription and secretion of IL-6 through NF-{kappa}B and AP-1 activation.

molecular biology↗

bioRxiv2025

SLC44A1 deficiency impedes myelin development in the central nervous system

Axon-wrapping myelin sheath is essential for the proper functioning of the central nervous system (CNS). Defects in myelination occur in various neurodevelopmental disorders. Human deficiency of the solute carrier 44A1 (SLC44A1) causes a new type of childhood-onset neurodegeneration with leukoencephalopathy. Currently, there is no effective treatment for this devastating disease, and little is known about its pathological mechanisms. In this study we identified that SLC44A1 is enriched in oligodendrocytes and required for myelin development in the CNS of zebrafish and rodents, which is crucial for normal motor coordination and cognitive function. Defective oligodendroglial maturation and myelinogenesis can be visualized by in vivo time-lapse imaging in the spinal cord of zebrafish with Slc44a1b deficiency. Mechanistically, SLC44A1 deficiency disrupts the expression of genes involved in phosphatidylcholine production pathway, and subsequently inhibiting phospholipid biosynthesis and disturbing the lipid composition of myelin sheaths. More importantly, supplementation with citicoline, a natural choline metabolite, restores developmental myelination in SLC44A1-deficient animals. These findings demonstrate that SLC44A1 is essential for CNS myelination and citicoline supplementation represents a potential therapeutic strategy to address the developmental hypomyelination.

neuroscience↗

bioRxiv2024

Brain-derived exosomal hemoglobin transfer contributes to neuronal mitochondrial homeostasis under hypoxia

Hypoxia is an important physiological stress causing nerve injuries and several brain diseases. However, the mechanism of brain response to hypoxia remains unclear, thus limiting the development of interventional strategies. This study conducted combined analyses of single-nucleus transcriptome sequencing and extracellular vesicle transcriptome sequencing on hypoxic mouse brains, described cell-cell communication in the brain under hypoxia from intercellular and extracellular dimensions, confirmed that hemoglobin mRNA was transferred from non-neuronal cells to neurons, and eventually expressed. Then we further explored the role of exosomal hemoglobin transfer in vitro, clarified that hypoxia promoted the transfer and expression of exosomal hemoglobin between endothelial cells and neurons. And we found the vital function of exosomal hemoglobin to protect against neurological injury by maintaining mitochondrial homeostasis in neurons. In conclusion, this study identified a novel mechanism of mutual aid in hypoxia responses in the brain, involving exosomal hemoglobin transfer, clarified the important role of exosomal communication in the process of brain stress response, and provided a novel interventional perspective for hypoxia-related brain diseases.

cell biology↗

bioRxiv2024

Ligand efficacy shifts a nuclear receptor conformational ensemble between transcriptionally active and repressive states

Nuclear receptors (NRs) are thought to dynamically alternate between transcriptionally active and repressive conformations, which are stabilized upon ligand binding. Most NR ligand series exhibit limited bias, primarily consisting of transcriptionally active agonists or neutral antagonists, but not repressive inverse agonists--a limitation that restricts understanding of the functional NR conformational ensemble. Here, we report a NR ligand series for peroxisome proliferator-activated receptor gamma (PPAR{gamma}) that spans a pharmacological spectrum from repression (inverse agonism) to activation (agonism) where subtle structural modifications switch compound activity. While crystal structures provide snapshots of the fully repressive state, NMR spectroscopy and conformation-activity relationship analysis reveals that compounds within the series shift the PPAR{gamma} conformational ensemble between transcriptionally active and repressive conformations that are populated in the apo/ligand-free ensemble. Our findings reveal a molecular framework for minimal chemical modifications that enhance PPAR{gamma} inverse agonism and elucidate their influence on the dynamic PPAR{gamma} conformational ensemble.

biophysics↗

bioRxiv2024

Role of Hepatocyte RIPK1 in Maintaining Liver Homeostasis during Metabolic Challenges

As a central hub for metabolism, the liver exhibits strong adaptability to maintain homeostasis in response to food fluctuations throughout evolution. However, the mechanisms governing this resilience remain incompletely understood. In this study, we identified Receptor interacting protein kinase 1 (RIPK1) in hepatocytes as a critical regulator in preserving hepatic homeostasis during metabolic challenges, such as short-term fasting or high-fat dieting. Our results demonstrated that hepatocyte-specific deficiency of RIPK1 sensitized the liver to short-term fasting-induced liver injury and hepatocyte apoptosis in both male and female mice. Despite being a common physiological stressor that typically does not induce liver inflammation, short-term fasting triggered hepatic inflammation and compensatory proliferation in hepatocyte-specific RIPK1-deficient (Ripk1{Delta}hep) mice. Transcriptomic analysis revealed that short-term fasting oriented the hepatic microenvironment into an inflammatory state in Ripk1{Delta}hep mice, with upregulated expression of inflammation and immune cell recruitment-associated genes. Single-cell RNA sequencing further confirmed the altered cellular composition in the liver of Ripk1{Delta}hep mice during fasting, highlighting the increased recruitment of macrophages to the liver. Mechanically, our results indicated that ER stress was involved in fasting-induced liver injury in Ripk1{Delta}hep mice. Overall, our findings revealed the role of RIPK1 in maintaining liver homeostasis during metabolic fluctuations and shed light on the intricate interplay between cell death, inflammation, and metabolism.

immunology↗

bioRxiv2024

Dysregulation of mitochondrial function by PLK1-mediated PDHA1 phosphorylation promotes Cr(VI)-associated lung cancer progression

Hexavalent chromium (Cr(VI)) is a class I environmental carcinogen known to induce lung epithelial cell transformation and promote lung cancer progression through alterations in the cell cycle and cellular energy metabolism. In this study, we investigated the role of polo-like kinase 1 (PLK1) in Cr(VI)-transformed (CrT) bronchial epithelial cells (BEAS-2B) and found that PLK1 expression was significantly upregulated in CrT cells, leading to impaired mitochondrial function and enhanced cell proliferation both in vitro and in vivo. High levels of PLK1 in CrT cells resulted in decreased mitochondrial activity due to defective modulation of pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1), which is crucial for pyruvate/Acetyl-CoA conversion and carbon influx into the tricarboxylic acid (TCA) cycle. Mechanistically, we demonstrated that PLK1 directly phosphorylates PDHA1 at T57, leading to E1 collapse and PDHA1 degradation via activation of mitophagy. These defects resulted in the inhibition of oxidative phosphorylation and reduction of mitochondrial superoxide generation, ultimately leading to suppression of mitochondrial-mediated apoptotic response. Our findings highlight the role of PLK1 in metabolic reprogramming during Cr(VI)-associated cancer progression, providing new insights and a potential therapeutic target to inhibit Cr(VI)-induced cancer development. Moreover, PLK1 inhibitors may also have the potential to increase chemo-sensitivity of cancer cells by restoring normal mitochondrial function, thereby mitigating drug resistance caused by mitochondrial dysfunction and hyperpolarization.

cancer biology↗

bioRxiv2024

Integrated analysis and systematic characterization of the regulatory network for human germline development

Primordial germ cells (PGCs) are the precursors of germline that are specified at embryonic stage. Recent studies reveal that humans employ different mechanisms for PGC specification compared with model organisms such as mice. Moreover, the specific regulatory machinery is still largely unexplored, mainly due to the inaccessible nature of this complex biological process. Here, we collect and integrate multi-omics data, including 581 RNA-seq, 54 ATAC-seq, 45 ChIP-seq, and 69 single-cell RNA-seq samples from different stages of human PGC development to recapitulate the precisely controlled and stepwise process, presenting an atlas in the human PGC database (hPGCdb). With these uniformly processed data and integrated analyses, we characterize the potential key transcription factors and regulatory networks governing human germ cell fate. We validate the important roles of some of the key factors in germ cell development by CRISPRi knockdown. We also identify the soma-germline interaction network and discover the involvement of SDC2 and LAMA4 for PGC development, as well as soma-derived NOTCH2 signaling for germ cell differentiation. Taken together, we have built a database for human PGCs and demonstrate that hPGCdb enables the identification of the missing pieces of mechanisms governing germline development, including both intrinsic and extrinsic regulatory programs.

developmental biology↗

bioRxiv2023

Functional characterization of RNA profiles in processing bodies of human embryonic stem cells and mesodermal cells

Processing bodies (P-bodies) are the membraneless organelles that play critical roles in RNA storage and decay. Abnormalities in P-bodies contribute to diseases and developmental disorders. Huge efforts have been applied to the identification of the protein components in P-bodies, however, the dynamics of RNA components of P-bodies in human embryonic stem cells (hESCs) during maintenance and differentiation remain largely elusive. Here, we characterized the RNA profiles of P-bodies from HEK293T cells, hESCs, and hESC-derived mesodermal cells. The number of P-bodies decreases upon hESC differentiation towards mesodermal fate, accompanied with the decreased RNAs within P-bodies. By functional analysis of the P-body enriched and P-body depleted genes across different cell types, we discovered the cell type-specific enrichment of P-body-genes and the potential association with human diseases. We also captured the non-coding RNAs, including long intergenic non-coding RNAs and transposable elements in P-bodies in a cell type-specific manner. Furthermore, we verified the involvement P-bodies in regulating the differentiation of hESCs towards mesoderm by over-expression of LSM14A and knocking down of SPTAN1. In summary, we characterized the mRNAs and non-coding RNAs in P-bodies of hESCs and hESC-derived mesodermal cells, discovering the potential roles that P-bodies play for the precise differentiation of hESCs.

developmental biology↗

bioRxiv2023

Covalent 14-3-3 Molecular Glues and Heterobifunctional Molecules Against Nuclear Transcription Factors and Regulators

14-3-3 proteins have the unique ability to bind and sequester a multitude of diverse phosphorylated signaling proteins and transcription factors. Many previous studies have shown that 14-3-3 interactions with specific phosphorylated substrate proteins can be enhanced through small-molecule natural product or fully synthetic molecular glue interactions. However, enhancing 14-3-3 interactions with both therapeutically intractable transcription factor substrates as well as potential neo-substrates to sequester and inhibit their function has remained elusive. One of the 14-3-3 proteins, 14-3-3{sigma} or SFN, has a cysteine C38 at the substrate binding interface near sites where previous 14-3-3 molecular glues have been found to bind. In this study, we screened a fully synthetic cysteine-reactive covalent ligand library to identify molecular glues that enhance interaction of 14-3-3{sigma} with not only druggable transcription factors such as estrogen receptor (ER), but also challenging oncogenic transcription factors such as YAP and TAZ that are part of the Hippo transducer pathway. We identified a hit EN171 that covalently targets 14-3-3 to enhance 14-3-3 interactions with ER, YAP, and TAZ leading to impaired estrogen receptor and Hippo pathway transcriptional activity. We further demonstrate that EN171 could not only be used as a molecular glue to enhance native protein interactions, but also could be used as a covalent 14-3-3 recruiter in heterobifunctional molecules to sequester nuclear neo-substrates such as BRD4 into the cytosol. Overall, our study reveals a covalent ligand that acts as a novel 14-3-3 molecular glue for challenging transcription factors such as YAP and TAZ and also demonstrates that these glues can be potentially utilized in heterobifunctional molecules to sequester nuclear neo-substrates out of the nucleus and into the cytosol to enable targeted protein localization.

biochemistry↗