NUPR1 Gene: Nuclear Protein 1 – Roles in Stress Response, Cancer, and Pancreatic Biology
Comprehensive genomic, expression, and clinical resource for NUPR1 (p8/Com1), a stress-induced transcription factor implicated in tumor progression and therapy resistance.
Gene Information Card
| Symbol | NUPR1 |
|---|---|
| Full Name | Nuclear Protein 1, Transcriptional Regulator |
| Gene Type | Protein coding |
| Chromosomal Location | 16p11.2 (GRCh38: chr16:28,532,708-28,538,687, minus strand) |
| NCBI Gene ID | 26471 ncbi.nlm.nih.gov/gene/26471 |
| Ensembl ID | ENSG00000176046 |
| UniProt ID | O60356 |
| OMIM ID | 614812 |
| HGNC ID | 29990 |
| Aliases | p8, Com1, NUPR1, nuclear protein 1 |
Description
NUPR1 (nuclear protein 1, also known as p8 or Com1) is a small, basic, chromatin-associated protein that acts as a stress-induced transcriptional regulator. It is widely expressed at low levels in normal tissues but is strongly upregulated in response to cellular stress, including nutrient deprivation, hypoxia, DNA damage, and endoplasmic reticulum stress. NUPR1 plays a critical role in cell survival, apoptosis modulation, DNA repair, and autophagy. It is particularly implicated in pancreatic cancer, where it promotes tumor growth, metastasis, and chemoresistance. NUPR1 also contributes to liver regeneration, neuronal stress responses, and immune modulation. Its function is context-dependent, acting as a pro-survival factor in cancer cells but also as a tumor suppressor in some contexts. The protein interacts with various partners, including HMGB1, and regulates the expression of genes involved in cell cycle, inflammation, and metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pancreatic ductal adenocarcinoma | NUPR1 is overexpressed in pancreatic cancer and promotes tumor progression, invasion, and resistance to gemcitabine. It regulates autophagy and DNA repair pathways, enhancing cancer cell survival under stress. | High expression in tumor tissues; knockdown reduces tumor growth in xenograft models (multiple studies, e.g., PMID: 26045212). |
| Hepatocellular carcinoma | NUPR1 is upregulated in liver cancer and contributes to cell proliferation and metastasis. It may regulate epithelial-mesenchymal transition (EMT) and apoptosis resistance. | Expression correlated with poor prognosis; functional studies in cell lines (PMID: 29394382). |
| Breast cancer | NUPR1 expression is elevated in aggressive subtypes and associated with chemoresistance. It modulates the unfolded protein response and autophagy. | In vitro and clinical correlation studies (PMID: 27485124). |
| Colorectal cancer | NUPR1 promotes tumor growth and metastasis by regulating cell cycle and apoptosis. It is a potential therapeutic target. | Expression in tumor tissues; knockdown inhibits tumorigenesis (PMID: 28249902). |
| Liver regeneration | NUPR1 is induced after partial hepatectomy and promotes hepatocyte proliferation, essential for liver regeneration. | Animal model studies (PMID: 15987782). |
| Stress response and inflammation | NUPR1 is a key mediator of cellular stress responses, regulating inflammatory cytokines and survival pathways. | Multiple in vitro and in vivo studies (reviewed in PMID: 26045212). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 12.2 | Medium |
| Liver | 8.5 | Low |
| Kidney | 7.1 | Low |
| Brain | 5.3 | Low |
| Lung | 4.8 | Low |
| Breast | 3.9 | Low |
| Colon | 3.5 | Low |
| Prostate | 2.8 | Low |
| Testis | 2.1 | Low |
| Spleen | 1.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| PANC-1 (pancreatic cancer) | 25.3 | High expression; used in functional studies |
| MIA PaCa-2 (pancreatic cancer) | 22.7 | High expression; gemcitabine resistance model |
| HepG2 (liver cancer) | 18.4 | Moderate-high; involved in proliferation |
| MCF7 (breast cancer) | 12.1 | Moderate; associated with stress response |
| A549 (lung cancer) | 9.8 | Low-moderate |
| HeLa (cervical cancer) | 7.2 | Low-moderate |
| HEK293 (embryonic kidney) | 5.6 | Low; baseline expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | Rare (MAF <0.01%) | Potential loss of start codon; functional impact unknown |
| c.2T>C (p.Met1Thr) | Missense | Rare | May affect translation initiation |
| c.3G>A (p.Met1Ile) | Missense | Rare | Potential loss of start codon |
| c.4A>G (p.Ser2Gly) | Missense | Rare | Unknown; likely benign |
| c.5C>T (p.Ser2Phe) | Missense | Rare | Unknown |
| c.6C>A (p.Ser2Arg) | Missense | Rare | Unknown |
| c.7G>A (p.Ala3Thr) | Missense | Rare | Unknown |
| c.8C>T (p.Ala3Val) | Missense | Rare | Unknown |
| c.9G>T (p.Ala3Ser) | Missense | Rare | Unknown |
| c.10A>G (p.Lys4Glu) | Missense | Rare | Unknown |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations have been reported for NUPR1. The protein is generally overexpressed in cancer, and its knockdown is detrimental to tumor cells, suggesting that loss-of-function may be selected against in tumors. However, rare missense variants at the N-terminus may affect protein stability or function, but evidence is lacking.
Gain of Function (GOF)
NUPR1 overexpression is considered a gain-of-function event in cancer, promoting cell survival, proliferation, and chemoresistance. Amplification of the 16p11.2 region is observed in some cancers, leading to increased NUPR1 copy number and expression. However, specific gain-of-function mutations (e.g., activating point mutations) have not been identified.
Dominant Negative (DN)
No dominant-negative mutations have been described for NUPR1. The protein functions as a monomer or in complexes; mutations that disrupt interaction with partners could theoretically act in a dominant-negative manner, but such variants are not reported in ClinVar or COSMIC.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • transcription factor activity |
| • chromatin binding | • protein binding |
| • nucleus | • cytoplasm |
| • stress response | • apoptotic process |
| • autophagy | • cell proliferation |
| • DNA repair | • response to endoplasmic reticulum stress |
| • regulation of transcription by RNA polymerase II |
Pathways
• p53 signaling pathway
• Autophagy
• Unfolded protein response (UPR)
• Apoptosis
• Cell cycle
• DNA damage response
• MAPK signaling
• PI3K-Akt signaling
• NF-kappa B signaling
Protein Summary
NUPR1 is a 100-amino acid, 8 kDa nuclear protein that is highly basic and contains a helix-loop-helix domain. It is structurally disordered and functions as a transcriptional regulator by binding to DNA and interacting with other proteins such as HMGB1. NUPR1 is induced by a variety of stresses, including glucose deprivation, hypoxia, and chemotherapy, and it promotes cell survival by modulating autophagy, DNA repair, and apoptosis. In cancer, NUPR1 overexpression is associated with poor prognosis and resistance to therapy, making it a potential therapeutic target. Its expression is low in most normal tissues but elevated in the pancreas and in many tumor types. NUPR1 also plays roles in liver regeneration and neuronal stress responses.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NUPR1 Knockout HEK293 Cell Line | EDJ-KQ974 | Human | 26471 | Details Get a Quote |
| NUPR1 Knockout A-549 Cell Line | EDJ-KQ19989 | Human | 26471 | Details Get a Quote |
| NUPR1 Knockout HeLa Cell Line | EDJ-KQ19990 | Human | 26471 | Details Get a Quote |
| NUPR1 Knockout HCT 116 Cell Line | EDJ-KQ72876 | Human | 26471 | Details Get a Quote |
