ArticleNature communications2022
pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- Mapping the functional dark proteome in cancer.Nature reviews. Cancer · 2026Review
- pTINCR Expression Is Associated with Tumor Aggressiveness but Does Not Independently Predict Prognosis in Head and Neck Cutaneous Squamous Cell Carcinoma.International journal of molecular sciences · 2026Article
- Noncoding RNA encoded peptides in tumors from discovery to mechanism and clinical translation.iScience · 2026Review
- Sketching microprotein portraits.Protein science : a publication of the Protein Society · 2026Review
- Microproteins in Human Physiology and Pathology.Biochemistry · 2026Review
- FAM65A, as a potential predictor of prognosis, promotes colorectal cancer progression via activating Ras/ERK/RSK signaling.iScience · 2026Article
- Recent advances in structural and functional diversities of cancer lncRNA-encoded peptides: current opportunities and challenges for enhancing cancer diagnosis and treatment.Cancer cell international · 2026Review
- Eukaryotic Microproteins.Annual review of biochemistry · 2025Review
- Beyond the Transcript: Translating Non-Coding RNAs and Their Impact on Cellular Regulation.Cancers · 2025Review
- Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significance.Molecular cancer · 2025Review
- Article
- A large-scale sORF screen identifies putative microproteins involved in cancer cell fitness.iScience · 2025Article
- Noncoding RNA-encoded peptides in cancer: biological functions, posttranslational modifications and therapeutic potential.Journal of hematology & oncology · 2025Review
- Emerging role of endogenous peptides encoded by non-coding RNAs in cancer biology.Non-coding RNA research · 2025Review
- Microproteins in cancer: identification, biological functions, and clinical implications.Trends in genetics : TIG · 2025Review
- Article
- Micropeptides Encoded by Noncoding RNAs: Biological Functions and Roles in Diseases.Research (Washington, D.C.) · 2025Review
- SUMOylation involved in malignant progression of multiple tumors and SENP5 may improve the chemotherapy sensitivity of hypoxic tumors.Frontiers in pharmacology · 2025Article
- Unraveling the critical role of SUMOylation in the governing of tumor immunity.Frontiers in immunology · 2025Review
- Pervasiveness of Microprotein Function AmongstCells · 2024Article
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Authors and funding
22 authors at 10 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human transcriptome contains thousands of small open reading frames (sORFs) that encode microproteins whose functions remain largely unexplored. Here, we show that TINCR lncRNA encodes pTINCR, an evolutionary conserved ubiquitin-like protein (UBL) expressed in many epithelia and upregulated upon differentiation and under cellular stress. By gain- and loss-of-function studies, we demonstrate that pTINCR is a key inducer of epithelial differentiation in vitro and in vivo. Interestingly, low expression of TINCR associates with worse prognosis in several epithelial cancers, and pTINCR overexpression reduces malignancy in patient-derived xenografts. At the molecular level, pTINCR binds to SUMO through its SUMO interacting motif (SIM) and to CDC42, a Rho-GTPase critical for actin cytoskeleton remodeling and epithelial differentiation. Moreover, pTINCR increases CDC42 SUMOylation and promotes its activation, triggering a pro-differentiation cascade. Our findings suggest that the microproteome is a source of new regulators of cell identity relevant for cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.