ArticleBMC biochemistry2003
Nuclear annexin II negatively regulates growth of LNCaP cells and substitution of ser 11 and 25 to glu prevents nucleo-cytoplasmic shuttling of annexin II.
Article in BMC biochemistry, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 66 citations in OpenAlex.
- ANXA2 in hepatocellular carcinoma: orchestrating tumorigenesis, progression, and therapeutic resistance toward precision targeting.Journal of translational medicine · 2025Review
- Annexin A2: A Double-Edged Sword in Pathogen Infection.Pathogens (Basel, Switzerland) · 2024Review
- Pathobiological functions and clinical implications of annexin dysregulation in human cancers.Frontiers in cell and developmental biology · 2022Review
- Molecular cloning and expression analysis of annexin A2 gene in sika deer antler tip.Asian-Australasian journal of animal sciences · 2018Article
- Annexin A2-mediated cancer progression and therapeutic resistance in nasopharyngeal carcinoma.Journal of biomedical science · 2018Review
- Functional Association between Regulatory RNAs and the Annexins.International journal of molecular sciences · 2018Review
- Reactive oxygen species exert opposite effects on Tyr23 phosphorylation of the nuclear and cortical pools of annexin A2.Journal of cell science · 2016Article
- Nuclear accumulation of annexin A2 contributes to chromosomal instability by coilin-mediated centromere damage.Oncogene · 2015Article
- Annexin A2 complexes with S100 proteins: structure, function and pharmacological manipulation.British journal of pharmacology · 2015Review
- A novel role of annexin A2 in human type I collagen gene expression.Journal of cellular biochemistry · 2015Article
- Cationic lipid guided short-hairpin RNA interference of annexin A2 attenuates tumor growth and metastasis in a mouse lung cancer stem cell model.Journal of controlled release : official journal of the Controlled Release Society · 2014Article
- The tumor suppressor annexin A10 is a novel component of nuclear paraspeckles.Cellular and molecular life sciences : CMLS · 2014Article
- Annexin A2: its molecular regulation and cellular expression in cancer development.Disease markers · 2014Review
- p11 and its role in depression and therapeutic responses to antidepressants.Nature reviews. Neuroscience · 2013Review
- Annexin A2 and S100A10 regulate human papillomavirus type 16 entry and intracellular trafficking in human keratinocytes.Journal of virology · 2013Article
- Annexin A2 heterotetramer: structure and function.International journal of molecular sciences · 2013Article
- Annexin A2 silencing induces G2 arrest of non-small cell lung cancer cells through p53-dependent and -independent mechanisms.The Journal of biological chemistry · 2012Article
- The association of annexin A2 and cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2012Article
- Genotoxic agents promote the nuclear accumulation of annexin A2: role of annexin A2 in mitigating DNA damage.PloS one · 2012Article
- Efficient nanoparticle mediated sustained RNA interference in human primary endothelial cells.Nanotechnology · 2011Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAnnexin II heavy chain (also called p36, calpactin I) is lost in prostate cancers and in a majority of prostate intraepithelial neoplasia (PIN). Loss of annexin II heavy chain appears to be specific for prostate cancer since overexpression of annexin II is observed in a majority of human cancers, including pancreatic cancer, breast cancer and brain tumors. Annexin II exists as a heterotetramer in complex with a protein ligand p11 (S100A10), and as a monomer. Diverse cellular functions are proposed for the two forms of annexin II. The monomer is involved in DNA synthesis. A leucine-rich nuclear export signal (NES) in the N-terminus of annexin II regulates its nuclear export by the CRM1-mediated nuclear export pathway. Mutation of the NES sequence results in nuclear retention of annexin II.
resultsAnnexin II localized in the nucleus is phosphorylated, and the appearance of nuclear phosphorylated annexin II is cell cycle dependent, indicating that phosphorylation may play a role in nuclear entry, retention or export of annexin II. By exogenous expression of annexin II in the annexin II-null LNCaP cells, we show that wild-type annexin II is excluded from the nucleus, whereas the NES mutant annexin II localizes in both the nucleus and cytoplasm. Nuclear retention of annexin II results in reduced cell proliferation and increased doubling time of cells. Expression of annexin II, both wild type and NES mutant, causes morphological changes of the cells. By site-specific substitution of glutamic acid in the place of serines 11 and 25 in the N-terminus, we show that simultaneous phosphorylation of both serines 11 and 25, but not either one alone, prevents nuclear localization of annexin II.
conclusionOur data show that nuclear annexin II is phosphorylated in a cell cycle-dependent manner and that substitution of serines 11 and 25 inhibit nuclear entry of annexin II. Aberrant accumulation of nuclear annexin II retards proliferation of LNCaP cells.
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