GO:0072739 response to anisomycin: Ribotoxic Stress Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0072739 (response to anisomycin) describes any cellular or organismal process that changes state or activity in response to an anisomycin stimulus, including movement, secretion, enzyme production and gene expression.
• Anisomycin is a ribosome-targeting antibiotic that stalls translation and triggers ribosome collisions, which activate general stress responses and the ribotoxic stress response [1,2].
• The ZAKα-driven ribotoxic stress response downstream of anisomycin can activate the human NLRP1 inflammasome, linking translation stress to innate immunity.
• Anisomycin selectively desensitizes stress kinase signalling and blocks fos and jun induction, making it a widely used tool to dissect MAPK-dependent immediate-early gene regulation.
• Anisomycin also regulates nucleocytoplasmic shuttling of transcriptional repressors and induces phosphorylation of small heat shock proteins such as alphaB-crystallin [4,8].
• CRISPR knockout, point-mutation, knock-in and overexpression cell models enable causal testing of genes acting in the response to anisomycin, supported by Ribo-seq, RNA-seq and proteomics.
Description
GO:0072739, response to anisomycin, is a biological process term in the Gene Ontology that captures any change in the state or activity of a cell or organism as a result of an anisomycin stimulus. Anisomycin is a bacterial antibiotic that binds the ribosome and inhibits peptide bond formation, and it is widely used experimentally to trigger translation stress and stress-activated signalling [1,6]. Because the term is defined by the stimulus rather than by a single pathway, it encompasses rapid signalling events, transcriptional reprogramming, protein phosphorylation and cell fate decisions that occur after anisomycin exposure [1,2,6]. For researchers, GO:0072739 is a useful annotation hub because anisomycin is a classic probe for ribotoxic stress, MAPK signalling and immediate-early gene induction. Ribosome collisions caused by anisomycin activate general stress responses that regulate cell fate, and in human cells the ZAKα-dependent ribotoxic stress response can activate the NLRP1 inflammasome [1,2]. Anisomycin also selectively desensitizes components of stress kinase activation and blocks fos and jun induction, which has made it a standard tool for dissecting AP-1 and MAPK-dependent transcription [6,7]. Beyond kinase signalling, anisomycin affects nuclear export of transcriptional repressors and induces phosphorylation of stress proteins such as alphaB-crystallin [4,8]. Even organism-level behavioural rhythms can be shifted by anisomycin, as shown by phase response curves in tau mutant hamsters. This breadth makes GO:0072739 relevant to cell biology, immunology, neuroscience and drug discovery, and it motivates the use of CRISPR-engineered cell models to test which genes are causally required for the response.
response to anisomycin At A Glance
| GO ID | GO:0072739 |
|---|---|
| GO term | response to anisomycin |
| Ontology | biological_process |
| Synonym | none listed in QuickGO |
| Definition | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an anisomycin stimulus. |
| Major function | Coordinates cellular responses to anisomycin-induced translation stress, including ribosome collision sensing, stress kinase signalling and gene expression changes [1,2,6]. |
| Stimulus | Anisomycin, a ribosome-targeting antibiotic that stalls translation and triggers ribotoxic stress [1,2]. |
| Representative pathways | Ribosome collision-triggered general stress responses, ZAKα-driven ribotoxic stress response, MAPK/JNK signalling and immediate-early gene regulation [1,2,6]. |
| Organism scope | Cell or organism level, including behavioural phase shifts in mammals. |
What Is GO:0072739?
In plain terms, GO:0072739 describes everything a cell or organism does after it encounters anisomycin. The official Gene Ontology definition states that it is any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an anisomycin stimulus. This is a biological process term, meaning it is defined by the stimulus and the resulting biological change rather than by a specific molecular function or cellular location. Anisomycin is a translation inhibitor, so the response typically begins with ribosome engagement and translation stress, then propagates through signalling cascades, gene expression changes and, in some settings, cell fate decisions [1,2,6].
Why Is response to anisomycin Important in Cell Biology?
GO:0072739 matters because anisomycin is one of the most widely used experimental triggers of translation stress and ribotoxic stress, and the resulting responses connect protein synthesis quality control to innate immunity, cell fate and gene regulation [1,2]. Understanding this term helps researchers interpret experiments that use anisomycin to probe MAPK signalling, immediate-early gene induction and inflammasome activation, and it provides a framework for identifying which genes are causally required for stress responses [2,6,7].
• Anisomycin stalls translation and causes ribosome collisions, activating general stress responses that help determine cell fate.
• The ZAKα-dependent ribotoxic stress response downstream of anisomycin activates the human NLRP1 inflammasome, linking translation stress to innate immunity.
• Anisomycin selectively desensitizes stress kinase signalling and blocks fos and jun induction, making it a key tool for studying MAPK-dependent transcription.
• Anisomycin regulates nuclear export of the Net repressor, connecting the response to nucleocytoplasmic transport and transcriptional control.
• Anisomycin induces phosphorylation of alphaB-crystallin, a small heat shock protein involved in stress adaptation.
• Anisomycin can shift behavioural phase in tau mutant hamsters, showing that the response can be studied at the organism level.
• Retinoic acid receptors inhibit AP1 activation by regulating ERK and CBP recruitment to AP1-responsive promoters, providing a mechanistic link between anisomycin-sensitive AP1 signalling and nuclear receptor crosstalk.
• JNK/MAPK signalling, which is engaged by anisomycin, is relevant to metabolic phenotypes such as hepatic steatosis and glucose intolerance in mice.
• CRISPR-engineered cell models allow causal testing of candidate genes in the response to anisomycin, from ribosome collision sensors to inflammasome components.
• The term supports drug discovery efforts targeting translation stress, ribotoxic stress and innate immune activation.
What Happens During response to anisomycin?
Anisomycin binding and translation stalling
In simple terms: Anisomycin first binds the ribosome and blocks protein synthesis, which is the initial trigger for the whole response.
Anisomycin is a ribosome-targeting antibiotic that inhibits translation, and this stalling is the primary stimulus for GO:0072739. Ribosome stalling leads to ribosome collisions, which are sensed by cellular quality control machinery and trigger general stress responses that regulate cell fate. This early step defines the stimulus-specific nature of the term and explains why anisomycin is used as a probe for translation stress [1,2].
Ribosome collision sensing and general stress responses
In simple terms: When ribosomes pile up on mRNA, cells detect the traffic jam and switch on stress programmes.
Ribosome collisions caused by anisomycin trigger general stress responses that help the cell cope with translation stress and decide whether to survive or die. These responses are part of the broader cellular reaction captured by GO:0072739 and provide a mechanistic basis for using anisomycin in studies of translation quality control and cell fate.
ZAKα-driven ribotoxic stress response and NLRP1 inflammasome activation
In simple terms: A kinase called ZAKα senses the ribotoxic stress and can switch on an immune alarm called the NLRP1 inflammasome.
In human cells, the ZAKα-driven ribotoxic stress response activated by anisomycin can activate the NLRP1 inflammasome, linking translation stress to innate immune signalling. This pathway is a key example of how the response to anisomycin extends beyond translation inhibition into inflammatory and immune processes, and it provides a rationale for studying GO:0072739 in immunology and inflammation research.
Stress kinase desensitization and immediate-early gene regulation
In simple terms: Anisomycin can also dampen some stress signalling pathways and block the induction of early response genes like fos and jun.
Anisomycin selectively desensitizes signalling components involved in stress kinase activation and blocks fos and jun induction, which has made it a classic tool for dissecting MAPK-dependent immediate-early gene regulation. Retinoic acid receptors can inhibit AP1 activation by regulating ERK and CBP recruitment to AP1-responsive promoters, illustrating how anisomycin-sensitive AP1 signalling intersects with nuclear receptor pathways. These effects are part of the gene expression changes that define GO:0072739 [6,7].
Nucleocytoplasmic transport and stress protein phosphorylation
In simple terms: The response also changes where certain proteins are located in the cell and adds phosphate tags to stress proteins.
Anisomycin regulates nuclear export of the Net repressor, showing that the response includes changes in nucleocytoplasmic transport of transcriptional regulators. In addition, anisomycin induces phosphorylation of alphaB-crystallin, a small heat shock protein, linking the response to stress protein modification. These events broaden the cellular activities covered by GO:0072739 beyond translation and kinase signalling [4,8].
Organism-level and behavioural responses
In simple terms: Anisomycin can even shift biological rhythms in animals, showing the response can be measured at the whole-organism level.
Phase response curves to anisomycin in tau mutant hamsters demonstrate that anisomycin can shift behavioural rhythms, providing an organism-level example of GO:0072739. This finding supports the definition of the term as applying to a cell or an organism and highlights its relevance to circadian and behavioural neuroscience.
Key Genes Involved in GO:0072739 response to anisomycin
The following genes and proteins are experimentally implicated in the response to anisomycin, based on the verified literature cited in this article.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ZAK (ZAKα) | Kinase that drives the ribotoxic stress response and can activate NLRP1 inflammasome after anisomycin | Central node for linking translation stress to innate immunity; candidate for knockout and point-mutation studies |
| NLRP1 | Inflammasome sensor activated downstream of ZAKα-driven ribotoxic stress | Readout of anisomycin-induced inflammation; useful for knock-in reporter and knockout models |
| MAPK8 (JNK1) | Stress kinase pathway engaged by anisomycin and relevant to JNK/MAPK signalling [3,6] | Target for dissecting stress kinase desensitization and metabolic phenotypes [3,6] |
| MAPK9 (JNK2) | Stress kinase pathway component in the JNK/MAPK response [3,6] | Candidate for knockout studies of anisomycin-sensitive signalling [3,6] |
| FOS | Immediate-early gene whose induction is blocked by anisomycin | Classic readout of anisomycin-sensitive transcription; useful for promoter reporter assays |
| JUN | Immediate-early gene whose induction is blocked by anisomycin | Marker of AP1-dependent transcription in response to anisomycin [6,7] |
| CRYAB (alphaB-crystallin) | Small heat shock protein phosphorylated in response to anisomycin | Stress protein readout; candidate for point-mutation studies of phosphorylation sites |
| NET (ELK3) | Transcriptional repressor regulated by nuclear export in response to anisomycin | Model for studying nucleocytoplasmic transport during the response |
| ERK (MAPK1/MAPK3) | Extracellular signal-regulated kinase involved in AP1 activation and CBP recruitment | Target for understanding crosstalk between anisomycin-sensitive AP1 and nuclear receptors |
| CBP (CREBBP) | Coactivator recruited to AP1-responsive promoters and regulated by retinoic acid receptors | Epigenetic/coactivator node in anisomycin-sensitive transcription |
| RARA | Retinoic acid receptor that inhibits AP1 activation via ERK and CBP regulation | Nuclear receptor model for modulating anisomycin responses |
| RARB | Retinoic acid receptor family member implicated in AP1 inhibition | Candidate for knockout studies of AP1 regulation |
| RARG | Retinoic acid receptor family member implicated in AP1 inhibition | Candidate for dissecting receptor-specific effects on anisomycin responses |
| Tau (MAPT) | Microtubule-associated protein; tau mutant hamsters show anisomycin phase response curves | Organism-level model for behavioural responses to anisomycin |
| Ribosome collision sensors (general) | Detect stalled and collided ribosomes after anisomycin | Upstream nodes for knockout and knock-in studies of translation stress |
| General stress response effectors | Mediate cell fate decisions downstream of ribosome collisions | Candidate genes for CRISPR screens in anisomycin-treated cells |
How Is response to anisomycin Regulated?
The response to anisomycin is regulated at multiple levels. At the stimulus level, anisomycin binding to the ribosome stalls translation and causes ribosome collisions, which activate general stress responses that regulate cell fate. Downstream, the ZAKα-driven ribotoxic stress response can activate the NLRP1 inflammasome, providing an immune regulatory layer. Anisomycin also selectively desensitizes stress kinase signalling and blocks fos and jun induction, indicating negative feedback and pathway-specific regulation of MAPK-dependent transcription. Retinoic acid receptors can inhibit AP1 activation by regulating ERK and CBP recruitment to AP1-responsive promoters, showing that nuclear receptor signalling can modulate the response. In addition, anisomycin regulates nuclear export of the Net repressor and induces phosphorylation of alphaB-crystallin, adding transport and stress-protein regulatory mechanisms [4,8]. JNK/MAPK signalling, which is engaged by anisomycin, is also relevant to metabolic regulation such as hepatic steatosis and glucose intolerance in mice.
response to anisomycin and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ZAK (ZAKα) | Innate immunity and inflammasome activation | Knockout and point-mutation cell lines with NLRP1 readouts |
| NLRP1 | Inflammatory and autoimmune signalling | Knock-in reporter and knockout models of inflammasome activation |
| MAPK8/MAPK9 (JNK) | Metabolic and stress signalling [3,6] | Knockout models for hepatic steatosis and glucose intolerance studies |
| FOS/JUN | Cancer and immediate-early gene regulation [6,7] | Promoter reporter and knockout cell lines for AP1 studies [6,7] |
| CRYAB (alphaB-crystallin) | Cellular stress adaptation | Point-mutation models of phosphorylation sites |
Innate immunity and inflammatory disease
The ZAKα-driven ribotoxic stress response activated by anisomycin can activate the human NLRP1 inflammasome, directly linking translation stress to innate immune activation. Dysregulated inflammasome activity is implicated in inflammatory and autoimmune conditions, so genes in this pathway are candidate therapeutic targets and experimental models of inflammation.
Cancer and cell fate control
Ribosome collisions triggered by anisomycin activate general stress responses that regulate cell fate, which is relevant to cancer biology because stress adaptation can influence survival versus death decisions in tumour cells. Anisomycin also blocks fos and jun induction and desensitizes stress kinase signalling, pathways that are frequently dysregulated in cancer [6,7].
Metabolic and stress-related phenotypes
JNK/MAPK signalling, which is engaged by anisomycin, has been linked to metabolic phenotypes such as hepatic steatosis and glucose intolerance in mice, suggesting that anisomycin-responsive pathways may be relevant to metabolic disease research. Stress protein phosphorylation, including alphaB-crystallin, further connects the response to cellular stress adaptation.
Neuroscience and behavioural rhythms
Anisomycin can shift behavioural phase in tau mutant hamsters, demonstrating that the response has organism-level consequences relevant to circadian and behavioural neuroscience. This provides a model for studying how translation stress affects neural and behavioural systems.
From response to anisomycin-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is ZAK required for anisomycin-induced NLRP1 inflammasome activation? | ZAK knockout cell line with inflammasome readouts |
| Which residues of NLRP1 are required for ribotoxic stress sensing? | NLRP1 point-mutation knock-in cell lines |
| Does loss of ribosome collision sensing alter cell fate after anisomycin? | Knockout of collision sensor genes followed by cell viability assays |
| How does anisomycin affect fos and jun induction? | FOS/JUN promoter reporter knock-in or knockout cell lines |
| Does alphaB-crystallin phosphorylation change stress survival? | CRYAB point-mutation knock-in models |
| Can overexpression of a candidate gene enhance or suppress the response? | Overexpression cell models treated with anisomycin [1,2] |
How to Study the response to anisomycin Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Ribo-seq | Ribosome occupancy and collisions | Detect translation stalling after anisomycin |
| RNA-seq | Transcriptional changes [6,7] | Measure fos/jun and AP1 target gene expression [6,7] |
| Phosphoproteomics | Protein phosphorylation events | Identify stress-induced modifications such as alphaB-crystallin |
| Western blot | Protein levels and phosphorylation [6,8] | Validate signalling and stress protein changes [6,8] |
| Immunofluorescence | Subcellular localization | Track nuclear export of repressors |
| Inflammasome assays | NLRP1 activation readouts | Test ZAK-dependent innate immune activation |
| Cell viability assays | Cell fate after stress | Assess survival versus death after anisomycin |
| Behavioural phase assays | Organism-level rhythm shifts | Study anisomycin effects in tau mutant hamsters |
Ribosome profiling (Ribo-seq)
Ribo-seq measures ribosome occupancy and can detect ribosome collisions and translation stalling caused by anisomycin, providing a direct readout of the initial stimulus in GO:0072739. It is typically applied to quantify global translation changes and identify genes whose translation is most affected.
RNA-seq and immediate-early gene analysis
RNA-seq measures gene expression changes after anisomycin treatment, including induction or blockade of immediate-early genes such as fos and jun [6,7]. It is used to define the transcriptional component of the response and to test how genetic perturbations alter it [6,7].
Proteomics and phosphoproteomics
Proteomics and phosphoproteomics can detect stress-induced modifications such as alphaB-crystallin phosphorylation and changes in signalling proteins after anisomycin exposure. These methods help map the post-translational events that accompany the response.
Imaging and subcellular localization
Imaging approaches can track nucleocytoplasmic transport of regulators such as the Net repressor in response to anisomycin, revealing spatial aspects of the response. They are typically applied to validate localization changes and to study stress granule or organelle dynamics.
How CRISPR Can Be Used to Study GO:0072739 response to anisomycin
Knockout
CRISPR knockout cell lines can remove candidate genes such as ZAK or NLRP1 to test whether they are required for anisomycin-induced ribotoxic stress and inflammasome activation. Knockouts of ribosome collision sensors can reveal which upstream factors are needed for general stress responses and cell fate decisions after anisomycin.
Point Mutation
Point-mutation knock-in models allow precise testing of phosphorylation sites or catalytic residues, for example in alphaB-crystallin or NLRP1, to determine which modifications are functionally important in the response to anisomycin [2,8]. These models help distinguish correlation from causation in stress signalling [2,8].
Knock-in
Knock-in of reporters or tags, such as fluorescent tags on FOS or JUN, enables real-time monitoring of immediate-early gene induction after anisomycin treatment [6,7]. Tagged knock-ins can also be used to track localization of regulators like the Net repressor during the response.
Overexpression
Overexpression cell models can test whether increasing the level of a candidate gene enhances or suppresses the response to anisomycin, for example by amplifying stress kinase signalling or inflammasome activation [1,2]. These models are useful for gain-of-function studies that complement knockout approaches [1,2].
How EDITGENE Supports response to anisomycin Research
Researchers studying response to anisomycin-related genes often need to determine whether a candidate gene is causally involved in translation stress sensing, stress kinase signalling or inflammasome activation, rather than merely correlated with the response. EDITGENE provides CRISPR-engineered cell models and screening services that allow such causal questions to be addressed directly in relevant cellular backgrounds.
Contact EDITGENE today to design your custom CRISPR model for response to anisomycin research.
Frequently Asked Questions About response to anisomycin
What is GO:0072739?
GO:0072739 is the Gene Ontology biological process term for response to anisomycin, defined as any process that results in a change in state or activity of a cell or an organism as a result of an anisomycin stimulus.
What is response to anisomycin?
Response to anisomycin describes the cellular or organismal changes that occur after exposure to anisomycin, a translation inhibitor that triggers ribosome collisions and stress signalling [1,2].
What genes are involved in response to anisomycin?
Genes implicated in the response include ZAK, NLRP1, MAPK8/MAPK9, FOS, JUN, CRYAB, NET, ERK, CBP and retinoic acid receptors, based on published studies [2,4,6,7,8].
How does anisomycin trigger stress responses?
Anisomycin stalls translation and causes ribosome collisions, which activate general stress responses and the ZAKα-driven ribotoxic stress response [1,2].
Does anisomycin activate the inflammasome?
Yes, the ZAKα-driven ribotoxic stress response activated by anisomycin can activate the human NLRP1 inflammasome.
Why does anisomycin block fos and jun induction?
Anisomycin selectively desensitizes signalling components involved in stress kinase activation, which blocks fos and jun induction.
Can anisomycin affect behaviour?
Yes, phase response curves to anisomycin in tau mutant hamsters show that it can shift behavioural rhythms.
What methods are used to study response to anisomycin?
Common methods include Ribo-seq, RNA-seq, phosphoproteomics, imaging, inflammasome assays and cell viability assays [1,2,4,6,8].
How can CRISPR help study response to anisomycin?
CRISPR knockout, point-mutation, knock-in and overexpression models allow causal testing of genes involved in translation stress sensing, signalling and inflammasome activation [1,2].
Is anisomycin relevant to human disease?
Anisomycin-responsive pathways connect to innate immunity, inflammation, cancer cell fate and metabolic signalling, making them relevant to several disease areas [1,2,3].
Conclusion
GO:0072739 response to anisomycin captures a rich biological process that begins with translation inhibition and ribosome collisions and extends to stress kinase signalling, immediate-early gene regulation, inflammasome activation and even organism-level behavioural changes [1,2,5,6]. The term is a valuable framework for interpreting experiments that use anisomycin as a probe of translation stress and stress signalling [1,2]. CRISPR-engineered cell models, combined with Ribo-seq, RNA-seq and proteomics, provide the causal evidence needed to move from correlation to mechanism in this pathway [1,2,6,8]. EDITGENE supports this work with knockout, point-mutation, knock-in, overexpression and library screening services tailored to response to anisomycin research.
References
- 1. Wu CC et al.. 2020. Ribosome Collisions Trigger General Stress Responses to Regulate Cell Fate.. Cell 182(2):404-416.e14 PMID: 32610081
- 2. Robinson KS et al.. 2022. ZAKα-driven ribotoxic stress response activates the human NLRP1 inflammasome.. Science 377(6603):328-335 PMID: 35857590
- 3. Fang Z et al.. 2023. Short-term tamoxifen administration improves hepatic steatosis and glucose intolerance through JNK/MAPK in mice.. Signal Transduct Target Ther 8(1):94 PMID: 36864030
- 4. Ducret C et al.. 1999. The net repressor is regulated by nuclear export in response to anisomycin, UV, and heat shock.. Mol Cell Biol 19(10):7076-87 PMID: 10490644
- 5. Mrosovsky N et al.. 1992. Phase response curve to anisomycin in tau mutant hamsters.. Experientia 48(9):875-7 PMID: 1397185
- 6. Hazzalin CA et al.. 1998. Anisomycin selectively desensitizes signalling components involved in stress kinase activation and fos and jun induction.. Mol Cell Biol 18(4):1844-54 PMID: 9528756
- 7. Benkoussa M et al.. 2002. Retinoic acid receptors inhibit AP1 activation by regulating extracellular signal-regulated kinase and CBP recruitment to an AP1-responsive promoter.. Mol Cell Biol 22(13):4522-34 PMID: 12052862
- 8. Ito H et al.. 1997. Phosphorylation of alphaB-crystallin in response to various types of stress.. J Biol Chem 272(47):29934-41 PMID: 9368070
