In this report, we present novel findings that implicate CCAAT/enhancer-binding protein (C/EBPalpha) in regulating the expression and activity of calpain 3 in vivo and data showing a new physiological substrate for calpain 3, cyclin A. Our results demonstrate that cleavage of cyclin A by calpain 3 occurs in mouse and human myeloid precursor cells. Calpain 3 cleaves cyclin A in vitro and in vivo, resulting in the production of a truncated product that lacks the N-terminal destruction box required for its degradation at the end of mitosis. The cleaved form of cyclin A retains the cyclin-dependent kinase (cdk) binding domain and forms active complexes with cdk2. Calpain 3-mediated cleavage of cyclin A is lacking in C/EBPalpha-/- mice, which are not able to produce mature granulocytes. Our data support a model in which calpain 3-mediated cleavage of cyclin A in dividing myeloid progenitor cells is important for the onset of differentiation. Deficits in this pathway in C/EBPalpha-/- mice might contribute to the failure of these mice to produce mature granulocytes. These data reveal a new pathway involving tightly controlled post-translational processing of cyclin A during differentiation of granulocytes.
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http://dx.doi.org/10.1074/jbc.M204096200 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Beijing Key Laboratory of Growth and Developmental Regulation for Protected Vegetable Crops, College of Horticulture, China Agricultural University, Beijing 100193, China.
Light serves as an energy source for cell division and expansion during fruit development. Cell expansion significantly influences fruit size and is closely linked to endoreduplication, a unique cell cycle variation characterized by DNA replication without cytokinesis. Paradoxically, under conditions of ample photosynthates, light signaling suppresses cell expansion.
View Article and Find Full Text PDFJ Ethnopharmacol
January 2025
Department of Veterinary Pathology, School of Veterinary Medicine, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.
Ethnopharmacological Relevance: Ceibapentandra (L.) Gaertn. (Malvaceae) has been used in Africa traditionally to manage a variety of illnesses, including cancer.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China.
Cholangiocarcinoma is a malignant tumor that emerges in the intrahepatic or extrahepatic bile ducts. Doramectin (DOR), a third-generation derivative of avermectins (AVMs), is renowned for its low toxicity and high efficiency. However, no research has hitherto focused on the anti-cholangiocarcinoma effects of these drugs.
View Article and Find Full Text PDFTurk J Biol
October 2024
Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, İstanbul, Turkiye.
Cell Div
December 2024
Institute for Research in Immunology and Cancer, Département de biochimie et médecine moléculaire, Université de Montréal, Montreal, Québec, Canada.
Background: Mitosis and cytokinesis are regulated by reversible phosphorylation events controlled by kinases and phosphatases. Drosophila Polo kinase, like its human ortholog PLK1, plays several roles in this process. Multiple mechanisms contribute to regulate Polo/PLK1 activity, localization and interactions.
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