ArticleMolecular and cellular biology2005
Binding of calmodulin to the carboxy-terminal region of p21 induces nuclear accumulation via inhibition of protein kinase C-mediated phosphorylation of Ser153.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- Subcellular compartmentalization dependent dichotomy of p21 in cancer.Molecular biology reports · 2026Review
- Let go or retain: role of calmodulin in orchestrating nuclear protein transport in eukaryotes.Plant cell reports · 2026Review
- The Emerging Role of p21 in Diabetes and Related Metabolic Disorders.International journal of molecular sciences · 2024Review
- CDKN1A/p21 in Breast Cancer: Part of the Problem, or Part of the Solution?International journal of molecular sciences · 2023Review
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- Article
- The Multifaceted p21 (Cip1/Waf1/Cancers · 2019Review
- Thr55 phosphorylation of p21 by MPK38/MELK ameliorates defects in glucose, lipid, and energy metabolism in diet-induced obese mice.Cell death & disease · 2019Article
- Evolutionary Approach of Intrinsically Disordered CIP/KIP Proteins.Scientific reports · 2019Article
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- Article
- Review
- Cooperative actions of p21WAF1 and p53 induce Slug protein degradation and suppress cell invasion.EMBO reports · 2014Article
- Inhibition of CRM1-dependent nuclear export sensitizes malignant cells to cytotoxic and targeted agents.Seminars in cancer biology · 2014Review
- PKA and PDE4D3 anchoring to AKAP9 provides distinct regulation of cAMP signals at the centrosome.The Journal of cell biology · 2012Article
- Nuclear export of proteins and drug resistance in cancer.Biochemical pharmacology · 2012Review
- CaM interaction and Ser181 phosphorylation as new K-Ras signaling modulators.Small GTPases · 2011Article
- CRL2(LRR-1) targets a CDK inhibitor for cell cycle control in C. elegans and actin-based motility regulation in human cells.Developmental cell · 2010Article
- K-Ras4B phosphorylation at Ser181 is inhibited by calmodulin and modulates K-Ras activity and function.Oncogene · 2010Article
- Calmodulin controls liver proliferation via interactions with C/EBPbeta-LAP and C/EBPbeta-LIP.The Journal of biological chemistry · 2010Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intracellular localization plays an important role in the functional regulation of the cell cycle inhibitor p21. We have previously shown that calmodulin binds to p21 and that calmodulin is essential for the nuclear accumulation of p21. Here, we analyze the mechanism of this regulation. We show that calmodulin inhibits in vitro phosphorylation of p21 by protein kinase C (PKC) and that this inhibition is dependent upon calmodulin binding to p21. Two-dimensional electrophoresis analysis of cells expressing the p21 wild type or p21S153A, a nonphosphorylatable mutant of p21 at position 153, indicates that Ser153 of p21 is a phosphorylable residue in vivo. Furthermore, Western blot analysis using phospho-Ser153-specific antibodies indicates that Ser153 phosphorylation in vivo is induced when PKC is activated and calmodulin is inhibited. The mutation of Ser153 to aspartate, a pseudophosphorylated residue, inhibits the nuclear accumulation of p21. Finally, whereas wild-type p21 translocates to the cytoplasm after PKC activation in the presence of calmodulin inhibitors, p21 carrying a nonphosphorylatable residue at position 153 remains in the nucleus. We propose that calmodulin binding to p21 prevents its phosphorylation by PKC at Ser153 and consequently allows its nuclear localization. When phosphorylated at Ser153, p21 is located at the cytoplasm and disrupts stress fibers.
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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.