ArticleMolecular and cellular biology2004
Protein kinase C delta blocks immediate-early gene expression in senescent cells by inactivating serum response factor.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 39 citations in OpenAlex.
- Unraveling Histone Loss in Aging and Senescence.Cells · 2024Review
- Narrative Review: Glucocorticoids in Alcoholic Hepatitis-Benefits, Side Effects, and Mechanisms.Journal of xenobiotics · 2022Review
- Progerin-Induced Replication Stress Facilitates Premature Senescence in Hutchinson-Gilford Progeria Syndrome.Molecular and cellular biology · 2017Article
- Involvement of the NFX1-repressor complex in PKC-δ-induced repression of hTERT transcription.Journal of biochemistry · 2016Article
- A conserved MADS-box phosphorylation motif regulates differentiation and mitochondrial function in skeletal, cardiac, and smooth muscle cells.Cell death & disease · 2015Article
- The Intricate Interplay between Mechanisms Underlying Aging and Cancer.Aging and disease · 2015Review
- Article
- MCL-1 localizes to sites of DNA damage and regulates DNA damage response.Cell cycle (Georgetown, Tex.) · 2010Article
- Cellular senescence: its role in tumor suppression and aging.Cancer science · 2009Review
- Histamine induces Egr-1 expression in human aortic endothelial cells via the H1 receptor-mediated protein kinase Cdelta-dependent ERK activation pathway.The Journal of biological chemistry · 2008Article
- An essential role for MCL-1 in ATR-mediated CHK1 phosphorylation.Molecular biology of the cell · 2008Article
- Irreversibility of cellular senescence: dual roles of p16INK4a/Rb-pathway in cell cycle control.Cell division · 2007Article
- High salt culture conditions inhibit serum- and NGF- but not PMA-induced Egr-1 gene transcription in rat C6 glioma cells.Journal of molecular neuroscience : MN · 2007Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibroblasts lose the ability to replicate in response to growth factors and become unable to express growth-associated immediate-early genes, including c-fos and egr-1, as they become senescent. The serum response factor (SRF), a major transcriptional activator of immediate-early gene promoters, loses the ability to bind to the serum response element (SRE) and becomes hyperphosphorylated in senescent cells. We identify protein kinase C delta (PKC delta) as the kinase responsible for inactivation of SRF both in vitro and endogenously in senescent cells. This is due to a higher level of PKC delta activity as cells age, production of the PKC delta catalytic fragment, and its nuclear localization in senescent but not in low-passage-number cells. The phosphorylation of T160 of SRF by PKC delta in vitro and in vivo led to loss of SRF DNA binding activity. Both the PKC delta inhibitor rottlerin and ectopic expression of a dominant negative form of PKC delta independently restored SRE-dependent transcription and immediate-early gene expression in senescent cells. Modulation of PKC delta activity in vivo with rottlerin or bistratene A altered senescent- and young-cell morphology, respectively. These observations support the idea that the coordinate transcriptional inhibition of several growth-associated genes by PKC delta contributes to the senescent phenotype.
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