Biology subjects

Hao, Y.-J.

Publications and source records attributed to Hao, Y.-J..

3 recordsLinked to original sources

bioRxiv2026

L-Lactate reprograms tumor-associated macrophages to drive pancreatic cancer progression via BCL3 lactylation

Metabolic reprogramming fuels pancreatic ductal adenocarcinoma (PDAC) malignancy, creating a nutrient-deprived and waste-rich microenvironment. How this extreme metabolic pressure dictates the phenotypic remodeling of infiltrating immune cells remains largely unclear. Metabolomic profiling of PDAC reveals that robust tumor glycolysis proceeds without a commensurate accumulation of extracellular lactate. Integrated single-cell profiling and tissue multiplex immunofluorescence demonstrate that tumor-associated macrophages (TAMs) act as the primary consumers of tumor-secreted lactate. The uptake of L-lactate directs macrophages toward a pro-tumorigenic state through site-specific L-lactylation of the transcriptional co-regulator BCL3 at lysine 21 (K21). Functioning as a molecular switch, K21 lactylation triggers BCL3 nuclear translocation and enhances its interaction with the NF-{kappa}B p50 subunit. The ensuing BCL3-p50 complex competitively displaces the pro-inflammatory p65 subunit, rewiring the transcriptional output to suppress inflammation and enforce tumor-supporting networks. In vivo, macrophage-specific expression of a lactylation-deficient BCL3 mutant (K21R) abolishes lactate-driven phenotypic shifts and restricts tumor growth. Clinically, a BCL3-lactylated macrophage signature spatially correlates with CD8+ T cell exclusion and predicts poor patient survival, providing a strong rationale for targeting the BCL3-lactylation axis to reverse TAM-driven PDAC progression. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/710237v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@173159eorg.highwire.dtl.DTLVardef@9065f3org.highwire.dtl.DTLVardef@153e0aorg.highwire.dtl.DTLVardef@9c2678_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2020

The apple palmitoyltransferase MdPAT16 regulates sugar content via an MdCBL1-MdCIPK13-MdSUT2.2 pathway

Protein palmitoylation, a post-translational protein modification, plays an important role in the regulation of substrate protein stability, protein interactions, and protein localization. It is generally believed that there are two mechanisms of palmitoylation: one by acyl-CoA and the other by protein acyltransferase (PAT). In this study, an MdPAT family member, MdPAT16, was identified and shown to have palmitoyltransferase activity. We found that this gene responded to salt stress and that its expression improved plant salt resistance. MdPAT16 was shown to interact with MdCBL1 and stabilize MdCBL1 protein levels through palmitoylation. MdPAT16 further regulated apple sugar content by stabilizing the MdCIPK13-MdSUT2.2 protein complex. We found that the N-terminal sequence of MdCBL1 contains a palmitoylation site and that the N-terminal deletion of MdCBL1 leads to changes in protein stability and subcellular localization. Finally, exogenous salt stress increased the interaction of MdPAT16 with MdCBL1 and the sugar content in apple. These findings suggest that MdPAT16 functions as a stable means for the palmitoylation of downstream protein. It may be a missing link in the plant salt stress response pathway and have an important impact on fruit quality.

plant biology↗

bioRxiv2019

BTB-TAZ domain protein MdBT2 modulates malate accumulation by targeting a bHLH transcription factor for degradation in response to nitrate

Excessive application of nitrate, an essential macronutrient and a signal regulating diverse physiological processes, decreases malate accumulation in apple fruit, but the underlying mechanism remains poorly understood. Here, we show that an apple BTB/TAZ protein MdBT2 is involved in regulating malate accumulation and vacuolar pH in response to nitrate. In vitro and in vivo assays indicate that MdBT2 interacts directly with and ubiquitinates a bHLH transcription factor, MdCIbHLH1, via the ubiquitin/26S proteasome pathway in response to nitrate. This ubiquitination results in the degradation of MdCIbHLH1 protein and reduces the transcription of MdCIbHLH1-targeted genes involved in malate accumulation and vacuolar acidification including MdVHA-A encoding a vacuolar H+-ATPase gene, and MdVHP1 encoding a vacuolar H+-pyrophosphatase gene, as well as MdALMT9 encoding a aluminum-activated malate transporter gene. A series of transgenic analyses in apple materials including fruits, plantlets and calli demonstrate that MdBT2 controls nitrate-mediated malate accumulation and vacuolar pH at least partially, if not completely, via regulating the MdCIbHLH1 protein level. Taken together, these findings reveal that MdBT2 regulates the stability of MdCIbHLH1 via ubiquitination in response to nitrate, which in succession transcriptionally reduces the expression of malate-associated genes, thereby controlling malate accumulation and vacuolar acidification in apples under high nitrate supply.

molecular biology↗