Interleukin-1α (IL-1α) is a dual-function proinflammatory mediator. In addition to its role in the canonical IL-1 signaling pathway, which employs membrane-bound receptors, a growing body of evidence shows that IL-1α has some additional intracellular functions. We identified the interaction of IL-1α with the tumor suppressor p53 in the nuclei and cytoplasm of both malignant and noncancerous mammalian cell lines using immunoprecipitation and the in situ proximity ligation assay (PLA). This interaction was enhanced by treatment with the antineoplastic drug etoposide, which suggests a role for the IL-1α•p53 interaction in genotoxic stress.

• MeSH
• cytoplazma metabolismus   MeSH
• dvouřetězcové zlomy DNA MeSH
• fluorescenční mikroskopie MeSH
• HeLa buňky MeSH
• imunoprecipitace MeSH
• interleukin-1alfa genetika   metabolismus   MeSH
• lidé MeSH
• nádorový supresorový protein p53 genetika   metabolismus   MeSH
• poškození DNA genetika   fyziologie   MeSH
• western blotting MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interleukin-1alfa MeSH
• nádorový supresorový protein p53 MeSH

Interleukin-1α (IL-1α) is a proinflammatory cytokine and a key player in host immune responses in higher eukaryotes. IL-1α has pleiotropic effects on a wide range of cell types, and it has been extensively studied for its ability to contribute to various autoimmune and inflammation-linked disorders, including rheumatoid arthritis, Alzheimer's disease, systemic sclerosis and cardiovascular disorders. Interestingly, a significant proportion of IL-1α is translocated to the cell nucleus, in which it interacts with histone acetyltransferase complexes. Despite the importance of IL-1α, little is known regarding its binding targets and functions in the nucleus. We took advantage of the histone acetyltransferase (HAT) complexes being evolutionarily conserved from yeast to humans and the yeast SAGA complex serving as an epitome of the eukaryotic HAT complexes. Using gene knock-out technique and co-immunoprecipitation of the IL-1α precursor with TAP-tagged subunits of the yeast HAT complexes, we mapped the IL-1α-binding site to the HAT/Core module of the SAGA complex. We also predicted the 3-D structure of the IL-1α N-terminal domain, and by employing structure similarity searches, we found a similar structure in the C-terminal regulatory region of the catalytic subunit of the AMP-activated/Snf1 protein kinases, which interact with HAT complexes both in mammals and yeast, respectively. This finding is further supported with the ability of the IL-1α precursor to partially rescue growth defects of snf1Δ yeast strains on media containing 3-Amino-1,2,4-triazole (3-AT), a competitive inhibitor of His3. Finally, the careful evaluation of our data together with other published data in the field allows us to hypothesize a new function for the ADA complex in SAGA complex assembly.

• MeSH
• biologické modely MeSH
• buněčné jádro metabolismus   MeSH
• genový knockout MeSH
• histonacetyltransferasy metabolismus   MeSH
• imunoprecipitace MeSH
• interleukin-1alfa chemie   metabolismus   MeSH
• lidé MeSH
• podjednotky proteinů metabolismus   MeSH
• protein-serin-threoninkinasy chemie   metabolismus   MeSH
• proteinkinasy aktivované AMP chemie   metabolismus   MeSH
• proteinové prekurzory chemie   metabolismus   MeSH
• Saccharomyces cerevisiae - proteiny metabolismus   MeSH
• Saccharomyces cerevisiae metabolismus   MeSH
• signální transdukce MeSH
• strukturní homologie proteinů MeSH
• subcelulární frakce metabolismus   MeSH
• terciární struktura proteinů MeSH
• trans-aktivátory metabolismus   MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• výpočetní biologie MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• histonacetyltransferasy MeSH
• interleukin-1alfa MeSH
• podjednotky proteinů MeSH
• protein-serin-threoninkinasy MeSH
• proteinkinasy aktivované AMP MeSH
• proteinové prekurzory MeSH
• Saccharomyces cerevisiae - proteiny MeSH
• SAGA complex, S cerevisiae MeSH Prohlížeč
• SNF1-related protein kinases MeSH Prohlížeč
• trans-aktivátory MeSH