Leucine Zipper Research Articles

SREBPs as the potential target for solving the polypharmacy dilemma.

The phenomenon of polypharmacy is a common occurrence among older people with multiple health conditions due to the rapid increase in population aging and the popularization of clinical guidelines. The prevalence of metabolic syndrome is growing quickly, representing a serious threat to both the public and the worldwide healthcare systems. In addition, it enhances the risk of cardiovascular disease as well as mortality and morbidity. Sterol regulatory element binding proteins (SREBPs) are basic helix-loop-helix leucine zipper transcription factors that transcriptionally modulate genes that regulate lipid biosynthesis and uptake, thereby serving an essential role in biological systems regulation. In this article, we have described the structure of SREBPs and explored their activation and regulation of signals. We also reveal that SREBPs are intricately involved in the modulation of metabolic diseases and thus have tremendous potential as the novel target for single-drug therapy for multiple diseases.

The role of basic leucine zipper transcription factor E4BP4 in cancer: a review and update.

Mutations in the genes of tumor cells and the disorder of immune microenvironment are the main factors of tumor development. The sensitivity of tumor cells to chemotherapy drugs affect the treatment of tumor. Nuclear transcription factor E4BP4 is dysregulated in a variety of malignant tumors. It can suppress the transcription of NFKBIA, RASSF8, SOSTDC1, FOXO-induced genes (TRAIL, FAS, GADD45a and GADD45b) and Hepcidin, up-regulate RCAN1-1 and PRNP, activate mTOR and p38 in cancer cells. Also, E4BP4 can regulate tumor immune microenvironment. TGFb1/Smad3/E4BP4/ IFNγ axis in NK cells plays an important role in antitumor immunotherapy. Over expression of E4BP4 inhibited the development of Th17 cells by directly binding to the RORγt promoter. Moreover, recent studies have shown that E4BP4 inhibited the expression of multidrug resistance genes. In this review, we summarize the molecular mechanism of E4BP4 in cancer cellular process, the effects of E4BP4 in cancer immunotherapy and antitumor drug resistance, to provide theoretical basis for tumor treatment strategies targeting E4BP4.

Heterogeneous nuclear ribonucleoprotein K promotes cap-independent translation initiation of retroviral mRNAs.

Translation initiation of the human immunodeficiency virus-type 1 (HIV-1) genomic mRNA (vRNA) is cap-dependent or mediated by an internal ribosome entry site (IRES). The HIV-1 IRES requires IRES-transacting factors (ITAFs) for function. In this study, we evaluated the role of the heterogeneous nuclear ribonucleoprotein K (hnRNPK) as a potential ITAF for the HIV-1 IRES. In HIV-1-expressing cells, the depletion of hnRNPK reduced HIV-1 vRNA translation. Furthermore, both the depletion and overexpression of hnRNPK modulated HIV-1 IRES activity. Phosphorylations and protein arginine methyltransferase 1 (PRMT1)-induced asymmetrical dimethylation (aDMA) of hnRNPK strongly impacted the protein's ability to promote the activity of the HIV-1 IRES. We also show that hnRNPK acts as an ITAF for the human T cell lymphotropic virus-type 1 (HTLV-1) IRES, present in the 5'UTR of the viral sense mRNA, but not for the IRES present in the antisense spliced transcript encoding the HTLV-1 basic leucine zipper protein (sHBZ). This study provides evidence for a novel role of the host hnRNPK as an ITAF that stimulates IRES-mediated translation initiation for the retroviruses HIV-1 and HTLV-1.

Evolutionary studies of the basic helix–loop–helix (bHLH) IVc gene family in plants and the role of AtILR3 in Arabidopsis response to ABA stress

AbstractThe basic helix–loop–helix (bHLH) IVc transcription factors (TFs) play central roles in controlling iron (Fe) homeostasis and biotic stress responses. However, their evolutions and functions in other abiotic stresses are poorly understood. In this study, the IAA‐LEUCINE RESISTANT3 (ILR3) homologs were traced roughly back to before the early origin of land plants and divided into six main clades (Clade A‐F). Further analysis found that the ILR3 orthologs were angiosperm‐specific, suffering from motif‐acquisition events and loose purifying selection. Synteny analysis displayed that the whole genome duplications (WGDs) contributed to the establishment of the IRON DEFICIENCY TOLERANT1 (IDT1, also called bHLH34)/bHLH104 lineage prior to the divergence of angiosperms. Sequence analysis revealed that the ILR3 homologs had some novel and conserved motifs except bHLH and leucine zipper (ZIP) domains. Particularly, Arabidopsis thaliana ILR3 (AtILR3) was a nuclear protein and greatly activated by ABA and CdCl2 stresses. Simultaneously, the molecular and genetic analyses suggested that the AtILR3 acted as a positive regulator in the ABA stress response through enhancing the ability of reactive oxygen species (ROS)‐scavenging, such as the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). The inductively coupled plasma mass spectrometry (ICP‐MS) analyses exhibited that the AtILR3 affected the absorption of nutrient elements, especially iron elements, under ABA stress. Collectively, our findings could shed deep light on the origin and evolution of the plant ILR3s, as well as the functions of the AtILR3 under ABA stress.

Baricitinib and tofacitinib off-target profile, with a focus on Alzheimer's disease.

Janus kinase (JAK) inhibitors were recently identified as promising drug candidates for repurposing in Alzheimer's disease (AD) due to their capacity to suppress inflammation via modulation of JAK/STAT signaling pathways. Besides interaction with primary therapeutic targets, JAK inhibitor drugs frequently interact with unintended, often unknown, biological off-targets, leading to associated effects. Nevertheless, the relevance of JAK inhibitors' off-target interactions in the context of AD remains unclear. Putative off-targets of baricitinib and tofacitinib were predicted using a machine learning (ML) approach. After screening scientific literature, off-targets were filtered based on their relevance to AD. Targets that had not been previously identified as off-targets of baricitinib or tofacitinib were subsequently tested using biochemical or cell-based assays. From those, active concentrations were compared to bioavailable concentrations in the brain predicted by physiologically based pharmacokinetic (PBPK) modeling. With the aid of ML and in vitro activity assays, we identified two enzymes previously unknown to be inhibited by baricitinib, namely casein kinase 2 subunit alpha 2 (CK2-α2) and dual leucine zipper kinase (MAP3K12), both with binding constant (K d) values of 5.8 μM. Predicted maximum concentrations of baricitinib in brain tissue using PBPK modeling range from 1.3 to 23nM, which is two to three orders of magnitude below the corresponding binding constant. In this study, we extended the list of baricitinib off-targets that are potentially relevant for AD progression and predicted drug distribution in the brain. The results suggest a low likelihood of successful repurposing in AD due to low brain permeability, even at the maximum recommended daily dose. While additional research is needed to evaluate the potential impact of the off-target interaction on AD, the combined approach of ML-based target prediction, in vitro confirmation, and PBPK modeling may help prioritize drugs with a high likelihood of being effectively repurposed for AD. This study explored JAK inhibitors' off-targets in AD using a multidisciplinary approach.We combined machine learning, in vitro tests, and PBPK modelling to predict and validate new off-target interactions of tofacitinib and baricitinib in AD.Previously unknown inhibition of two enzymes (CK2-a2 and MAP3K12) by baricitinib were confirmed using in vitro experiments.Our PBPK model indicates that baricitinib low brain permeability limits AD repurposing.The proposed multidisciplinary approach optimizes drug repurposing efforts in AD research.

Walnut phosphatase 2A proteins interact with basic leucine zipper protein JrVIP1 to regulate osmotic stress response via calcium signaling

Walnut phosphatase 2A proteins interact with basic leucine zipper protein JrVIP1 to regulate osmotic stress response via calcium signaling

Heterodimeric interaction of the C/S1 basic leucine zipper transcription factors in black raspberry: a genome-wide identification and comparative analysis

Heterodimeric interaction of the C/S1 basic leucine zipper transcription factors in black raspberry: a genome-wide identification and comparative analysis

Parallel Evolution of Transcription Factors in Basal Metazoans.

Transcription factors (TFs) play a pivotal role as regulators of gene expression, orchestrating the formation and maintenance of diverse animal body plans and innovations. However, the precise contributions of TFs and the underlying mechanisms driving the origin of basal metazoan body plans, particularly in ctenophores, remain elusive. Here, we present a comprehensive catalog of TFs in 2 ctenophore species, Pleurobrachia bachei and Mnemiopsis leidyi, revealing 428 and 418 TFs in their respective genomes. In contrast, morphologically simpler metazoans have a reduced TF representation compared to ctenophores, cnidarians, and bilaterians: the sponge Amphimedon encodes 277 TFs, and the placozoan Trichoplax adhaerens encodes 274 TFs. The emergence of complex ctenophore tissues and organs coincides with significant lineage-specific diversification of the zinc finger C2H2 (ZF-C2H2) and homeobox superfamilies of TFs. Notable, the lineages leading to Amphimedon and Trichoplax exhibit independent expansions of leucine zipper (BZIP) TFs. Some lineage-specific TFs may have evolved through the domestication of mobile elements, thereby supporting alternative mechanisms of parallel TF evolution and body plan diversification across the Metazoa.

Retracted: Ablation of Basic Leucine Zipper Transcription Factor ATF-Like Potentiates Estradiol to Induce Atopic Dermatitis.

[This retracts the article DOI: 10.1155/2022/7024669.].

Interferon regulatory factor 4 plays a pivotal role in the development of aGVHD-associated colitis

ABSTRACT Interferon regulatory factor 4 (IRF4) is a master transcription factor that regulates T helper cell (Th) differentiation. It interacts with the Basic leucine zipper transcription factor, ATF-like (BATF), depletion of which in CD4+ T cells abrogates acute graft-versus-host disease (aGVHD)-induced colitis. Here, we investigated the immune-regulatory role of Irf4 in a mouse model of MHC-mismatched bone marrow transplantation. We found that recipients of allogenic Irf4 -/- CD4+ T cells developed less GVHD-related symptoms. Transcriptome analysis of re-isolated donor Irf4 -/- CD4+ T helper (Th) cells, revealed gene expression profiles consistent with loss of effector T helper cell signatures and enrichment of a regulatory T cell (Treg) gene expression signature. In line with these findings, we observed a high expression of the transcription factor BTB and CNC homolog 2; (BACH2) in Irf4 -/- T cells, which is associated with the formation of Treg cells and suppression of Th subset differentiation. We also found an association between BACH2 expression and Treg differentiation in patients with intestinal GVHD. Finally, our results indicate that IRF4 and BACH2 act as counterparts in Th cell polarization and immune homeostasis during GVHD. In conclusion, targeting the BACH2/IRF4-axis could help to develop novel therapeutic approaches against GVHD.

Interactome Analysis Identifies the Role of BZW2 in Promoting Endoplasmic Reticulum-Mitochondria Contact and Mitochondrial Metabolism

Understanding the molecular functions of less-studied proteins is an important task of life science research. Despite reports of basic leucine zipper and W2 domain-containing protein 2 (BZW2) promoting cancer progression first emerging in 2017, little is known about its molecular function. Using a quantitative proteomic approach to identify its interacting proteins, we found that BZW2 interacts with both endoplasmic reticulum (ER) and mitochondrial proteins. We thus hypothesized that BZW2 localizes to and promotes the formation of ER-mitochondria contact sites and that such localization would promote calcium transport from ER to the mitochondria and promote ATP production. Indeed, we found that BZW2 localized to ER-mitochondria contact sites and that BZW2 knockdown decreased ER-mitochondria contact, mitochondrial calcium levels, and ATP production. These findings provide key insights into molecular functions of BZW2, the potential role of BZW2 in cancer progression, and highlight the utility of interactome data in understanding the function of less-studied proteins.

PrLZ regulates EMT and invasion in prostate cancer via the TGF-β1/p-smad2/miR-200 family/ZEB1 axis.

Prostate leucine zipper (PrLZ) is a prostate-specific protein, and our previous study demonstrated that PrLZ enhances the malignant progression of prostate cancer (Pca). However, the roles of PrLZ in epithelial to mesenchymal transition (EMT) remain unknown. Quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) staining, hematoxylin-eosin (HE) staining, and western blotting were used to analyze the expression of protein and genes level in human PCa cell lines. Invasion assay was used to examine the effect of PrLZ, miR-200a, miR-200b, miR-200c, miR-141, miR-429, miR-205, and ZEB1 on PCa cell line invasion in vitro. Prostate cancer metastasis animal model was designed to assess the effect of PrLZ on PCa cell line invasion in vivo. We proved that high PrLZ expression initiates EMT, which was shown by the downregulation of E-cadherin and upregulation of vimentin in PC-3/PrLZ and ARCaP-E/PrLZ cells. Mechanistic analysis revealed that PrLZ regulates EMT by activating TGF-β1/p-smad2 signaling and further inhibiting the expression of miR-200 family members, which negatively regulates ZEB1 expression and causes EMT in Pca. Moreover, using two of orthotopic mouse model and tail vein injection of human prostate cancer cells mouse model, we observed that PC-3/PrLZ cells led to the development of distant organ metastases in vivo. Our results show the mechanism by which PrLZ regulates EMT and metastasis and suggest that PrLZ may be a potential therapeutic target for Pca metastasis.

GASZ self-interaction clusters mitochondria into the intermitochondrial cement for proper germ cell development.

Mitochondrial features and activities vary in a cell type- and developmental stage-dependent manner to critically impact cell function and lineage development. Particularly in male germ cells, mitochondria are uniquely clustered into intermitochondrial cement (IMC), an electron-dense granule in the cytoplasm to support proper spermatogenesis. But it remains puzzling how mitochondria assemble into such a stable structure as IMC without limiting membrane during development. Here, we showed that GASZ (germ cell-specific, ankyrin repeat, SAM and basic leucine zipper domain containing protein), a mitochondrion-localized germ cell-specific protein, self-interacted with each other to cluster mitochondria and maintain protein stability for IMC assembling. When the self-interaction of GASZ was disrupted by either deleting its critical interaction motif or using a blocking peptide, the IMC structure was destabilized, which in turn led to impaired spermatogenesis. Notably, the blocked spermatogenesis was reversible once GASZ self-interaction was recovered. Our findings thus reveal a critical mechanism by which mitochondrion-based granules are properly assembled to support germ cell development while providing an alternative strategy for developing nonhormonal male contraceptives by targeting IMC protein interactions.

Preclinical assessment of an anti-HTLV-1 heterologous DNA/MVA vaccine protocol expressing a multiepitope HBZ protein

BackgroundHuman T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available treatments and the challenge in developing a protective vaccine highlight the need to produce effective immunotherapeutic tools. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ) plays an important role in the HTLV-1 persistence, conferring a survival advantage to infected cells by reducing the HTLV-1 proteins expression, allowing infected cells to evade immune surveillance, and enhancing cell proliferation leading to increased proviral load.MethodsWe have generated a recombinant Modified Virus Vaccinia Ankara (MVA-HBZ) and a plasmid DNA (pcDNA3.1(+)-HBZ) expressing a multiepitope protein based on peptides of HBZ to study the immunogenic potential of this viral-derived protein in BALB/c mice model. Mice were immunized in a prime-boost heterologous protocol and their splenocytes (T CD4+ and T CD8+) were immunophenotyped by flow cytometry and the humoral response was evaluated by ELISA using HBZ protein produced in prokaryotic vector as antigen.ResultsT CD4+ and T CD8+ lymphocytes cells stimulated by HBZ-peptides (HBZ42–50 and HBZ157–176) showed polyfunctional double positive responses for TNF-α/IFN-γ, and TNF-α/IL-2. Moreover, T CD8+ cells presented a tendency in the activation of effector memory cells producing granzyme B (CD44+High/CD62L−Low), and the activation of Cytotoxic T Lymphocytes (CTLs) and cytotoxic responses in immunized mice were inferred through the production of granzyme B by effector memory T cells and the expression of CD107a by CD8+ T cells. The overall data is consistent with a directive and effector recall response, which may be able to operate actively in the elimination of HTLV-1-infected cells and, consequently, in the reduction of the proviral load. Sera from immunized mice, differently from those of control animals, showed IgG-anti-HBZ production by ELISA.ConclusionsOur results highlight the potential of the HBZ multiepitope protein expressed from plasmid DNA and a poxviral vector as candidates for therapeutic vaccine.

Transcriptional regulatory mechanisms of flavonoid metabolism from flower bud to flower in Hemerocallis citrina

The flower buds of Hemerocallis citrina are well-known functional foods in East Asian countries for their promoting intelligence and forgetting worries, in which their nutrients, especially flavonoids, play an important role. However, they will be discarded when the buds develop into flowers, part of the reason is the type and content of flavonoids change considerably. At present, the developmental mechanism responsible for these differences is still unclear. Based on "multi-omics" technologies, the results of this study revealed that 18 flavonoids were significantly differential, including five flavonoids, eight flavonols and three flavanones, one isoflavone and one anthocyanin, and their biosynthesis involved 50 differential genes and 25 differential enzyme proteins. Among them, nine genes encoding four key enzymes (chalcone isomerase, isoflavone 2′-hydroxylase, flavonol-3-O-l-rhamnoside-7-O-glucosyltransferase and phlorizin synthase) were targeted by seven conserved miRNA (microRNA) families, covering miR394, miR477, miR396, miR528, miR164, miR395 and miR447. Furthermore, 10 genes encoding five transcription factor families (bZIP (basic leucine zipper), NAC (NAM, ATAF1/2 and CUC2), GRAS (GAI, RGA and SCR), TCP (TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR) and MADS (MCM1/AGAMOUS/DEFICIENS/SRF)) were targeted by seven conserved miRNA families, including miR393, miR166, miR171, miR477, miR164, miR528 and miR447. They are jointly involved in the metabolic regulation of flavone and flavonol biosynthesis, isoflavonoid biosynthesis, and flavonoid biosynthesis from flower buds to flowering development of H. citrina.

Role of bZIP Transcription Factors in Response to NaCl Stress in Tamarix ramosissima under Exogenous Potassium (K+).

Salt stress is a significant environmental factor affecting plant growth and development, with NaCl stress being one of the most common types of salt stress. The halophyte, Tamarix ramosissima Ledeb (T. ramosissima), is frequently utilized for the afforestation of saline-alkali soils. Indeed, there has been limited research and reports by experts and scholars on the regulatory mechanisms of basic leucine zipper (bZIP) genes in T. ramosissima when treated with exogenous potassium (K+) to alleviate the effects of NaCl stress. This study focused on the bZIP genes in T. ramosissima roots under NaCl stress with additional KCl applied. We identified key candidate genes and metabolic pathways related to bZIP and validated them through quantitative real-time PCR (qRT-PCR). The results revealed that under NaCl stress with additional KCl applied treatments at 0 h, 48 h, and 168 h, based on Pfam protein domain prediction and physicochemical property analysis, we identified 20 related bZIP genes. Notably, four bZIP genes (bZIP_2, bZIP_6, bZIP_16, and bZIP_18) were labeled with the plant hormone signal transduction pathway, showing a predominant up-regulation in expression levels. The results suggest that these genes may mediate multiple physiological pathways under NaCl stress with additional KCl applied at 48 h and 168 h, enhancing signal transduction, reducing the accumulation of ROS, and decreasing oxidative damage, thereby enhancing the tolerance of T. ramosissima to NaCl stress. This study provides gene resources and a theoretical basis for further breeding of salt-tolerant Tamarix species and the involvement of bZIP transcription factors in mitigating NaCl toxicity.

The E3 ligase TaGW2 mediates transcription factor TaARR12 degradation to promote drought resistance in wheat.

Drought stress limits crop yield, but the molecular modulators and their mechanisms underlying the trade-off between drought resistance and crop growth and development remain elusive. Here, a grain width and weight2 (GW2)-like really interesting new gene finger E3 ligase, TaGW2, was identified as a pivotal regulator of both kernel development and drought responses in wheat (Triticum aestivum). TaGW2 overexpression enhances drought resistance but leads to yield drag under full irrigation conditions. In contrast, TaGW2 knockdown or knockout attenuates drought resistance but remarkably increases kernel size and weight. Furthermore, TaGW2 directly interacts with and ubiquitinates the type-B Arabidopsis response regulator TaARR12, promoting its degradation via the 26S proteasome. Analysis of TaARR12 overexpression and knockdown lines indicated that TaARR12 represses the drought response but does not influence grain yield in wheat. Further DNA affinity purification sequencing combined with transcriptome analysis revealed that TaARR12 downregulates stress-responsive genes, especially group-A basic leucine zipper (bZIP) genes, resulting in impaired drought resistance. Notably, TaARR12 knockdown in the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9)-mediated tagw2 knockout mutant leads to significantly higher drought resistance and grain yield compared to wild-type plants. Collectively, these findings show that the TaGW2-TaARR12 regulatory module is essential for drought responses, providing a strategy for improving stress resistance in high-yield wheat varieties.

Cucumis sativus CsbZIP90 suppresses Podosphaera xanthii resistance by modulating reactive oxygen species

Resistance to disease in plants requires the coordinated action of multiple functionally related genes, as it is difficult to improve disease resistance with a single functional gene. Therefore, the use of transcription factors to regulate the expression of multiple resistance genes to improve disease resistance has become a recent focus in the field of gene research. The basic leucine zipper (bZIP) transcription factor family plays vital regulatory roles in processes, such as plant growth and development and the stress response. In our previous study, CsbZIP90 (Cucsa.134370) was involved in the defense response of cucumber to Podosphaera xanthii, but the relationship between cucumber and resistance to powdery mildew remained unclear. Herein, we detected the function of CsbZIP90 in response to P. xanthii. CsbZIP90 was localized to the cytoplasm and nucleus, and its expression was significantly induced during P. xanthii attack. Transient overexpression of CsbZIP90 in cucumber cotyledons resulted in decreased resistance to P. xanthii, while silencing CsbZIP90 increased resistance to P. xanthii. CsbZIP90 negatively regulated the expression of reactive oxygen species (ROS)-related genes and activities of ROS-related kinases. Taken together, our results show that CsbZIP90 suppresses P. xanthi resistance by modulating ROS. This study will provide target genes for breeding cucumbers resistant to P. xanthii.

Characterization of the basic leucine zipper transcription factor family of Neoporphyra haitanensis and its role in acclimation to dehydration stress

BackgroundNeoporphyra haitanensis, a major marine crop native to southern China, grows in the harsh intertidal habitats of rocky coasts. The thallus can tolerate fluctuating and extreme environmental stresses, for example, repeated desiccation/rehydration due to the turning tides. It is also a typical model system for investigating stress tolerance mechanisms in intertidal seaweed. The basic leucine zipper (bZIP) transcription factors play important roles in the regulation of plants’ responses to environmental stress stimuli. However, little information is available regarding the bZIP family in the marine crop Nh. haitanensis.ResultsWe identified 19 bZIP genes in the Nh. haitanensis genome and described their conserved domains. Based on phylogenetic analysis, these 19 NhhbZIP genes, distributed unevenly on the 11 superscaffolds, were divided into four groups. In each group, there were analogous exon/intron numbers and motif compositions, along with diverse exon lengths. Cross-species collinearity analysis indicated that 17 and 9 NhhbZIP genes were orthologous to bZIP genes in Neopyropia yezoensis and Porphyra umbilicalis, respectively. Evidence from RNA sequencing (RNA-seq) data showed that the majority of NhhbZIP genes (73.68%) exhibited transcript abundance in all treatments. Furthermore, genes NN 2, 4 and 5 showed significantly altered expression in response to moderate dehydration, severe dehydration, and rehydration, respectively. Gene co-expression network analysis of the representative genes was carried out, followed by gene set enrichment analysis. Two NhhbZIP genes collectively responding to dehydration and rehydration and their co-expressing genes mainly participated in DNA repair, DNA metabolic process, and regulation of helicase activity. Two specific NhhbZIP genes responding to severe dehydration and their corresponding network genes were mainly involved in macromolecule modification, cellular catabolic process, and transmembrane transport. Three specific NhhbZIP genes responding to rehydration and their co-expression gene networks were mainly involved in the regulation of the cell cycle process and defense response.ConclusionsThis study provides new insights into the structural composition, evolution, and function of the NhhbZIP gene family. Our results will help us to further study the functions of bZIP genes in response to dehydration and rehydration in Nh. haitanensis and improve Nh. haitanensis in southern China.

The bZIP transcription factor ATF1 regulates blue light and oxidative stress responses in Trichoderma guizhouense

AbstractIn several filamentous fungi, incident light and environmental stress signaling share the mitogen‐activated protein kinase (MAPK) HOG (SAK) pathway. It has been revealed that short‐term illumination with blue light triggers the activation of the HOG pathway in Trichoderma spp. In this study, we demonstrate the crucial role of the basic leucine zipper transcription factor ATF1 in blue light responses and signaling downstream of the MAPK HOG1 in Trichoderma guizhouense. The lack of ATF1 severely impaired photoconidiation and delayed vegetative growth and conidial germination. Upon blue light or H2O2 stimuli, HOG1 interacted with ATF1 in the nucleus. Genome‐wide transcriptome analyses revealed that 61.8% (509 out of 824) and 85.2% (702 out of 824) of blue light‐regulated genes depended on ATF1 and HOG1, respectively, of which 58.4% (481 out of 824) were regulated by both of them. Our results also show that blue light promoted conidial germination and HOG1 and ATF1 played opposite roles in controlling conidial germination in the dark. Additionally, the lack of ATF1 led to reduced oxidative stress resistance, probably because of the downregulation of catalase‐encoding genes. Overall, our results demonstrate that ATF1 is the downstream component of HOG1 and is responsible for blue light responses, conidial germination, vegetative growth, and oxidative stress resistance in T. guizhouense.