ArticleMolecular and cellular biology2002
Cell attachment to the extracellular matrix induces proteasomal degradation of p21(CIP1) via Cdc42/Rac1 signaling.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 80 citations in OpenAlex.
- Subcellular compartmentalization dependent dichotomy of p21 in cancer.Molecular biology reports · 2026Review
- Photobiomodulation Modulates Proliferation and Gene Expression Related to Calcium Signaling in Human Osteoblast Cells.Journal of lasers in medical sciences · 2024Article
- Targeting the secreted RGDKGE collagen fragment reduces PD‑L1 by a proteasome‑dependent mechanism and inhibits tumor growth.Oncology reports · 2023Article
- FcεRI-HDAC3-MCP1 Signaling Axis Promotes Passive Anaphylaxis Mediated by Cellular Interactions.International journal of molecular sciences · 2019Review
- Activation of Cell Surface Bound 20S Proteasome Inhibits Vascular Cell Growth and Arteriogenesis.BioMed research international · 2015Article
- P21 activated kinases: structure, regulation, and functions.Small GTPases · 2014Review
- Biological effects of low level laser therapy.Journal of lasers in medical sciences · 2014Review
- p104 binds to Rac1 and reduces its activity during myotube differentiation of C2C12 cell.TheScientificWorldJournal · 2014Article
- Histone deacetylase 3 mediates allergic skin inflammation by regulating expression of MCP1 protein.The Journal of biological chemistry · 2012Article
- PAK4-6 in cancer and neuronal development.Cellular logistics · 2012Article
- The pak4 protein kinase in breast cancer.ISRN oncology · 2012Article
- Integrin-mediated cell attachment induces a PAK4-dependent feedback loop regulating cell adhesion through modified integrin alpha v beta 5 clustering and turnover.Molecular biology of the cell · 2010Article
- Functional stability of rescued delta F508 cystic fibrosis transmembrane conductance regulator in airway epithelial cells.American journal of respiratory cell and molecular biology · 2010Article
- Anchorage-independent growth of pocket protein-deficient murine fibroblasts requires bypass of G2 arrest and can be accomplished by expression of TBX2.Molecular and cellular biology · 2008Article
- Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation.Molecular cell · 2008Article
- Oncogenic H-Ras V12 promotes anchorage-independent cytokinesis in human fibroblasts.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Simvastatin inactivates beta1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells.Cancer science · 2007Article
- The proteasome inhibitor lactacystin attenuates growth and migration of vascular smooth muscle cells and limits the response to arterial injury.Experimental and clinical cardiology · 2007Article
- Focal adhesion kinase controls cellular levels of p27/Kip1 and p21/Cip1 through Skp2-dependent and -independent mechanisms.Molecular and cellular biology · 2006Article
- E-cadherin engagement stimulates proliferation via Rac1.The Journal of cell biology · 2006Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cyclin-dependent kinase 2 (Cdk2) inhibitors p21(CIP1) and p27(KIP1) are negatively regulated by anchorage during cell proliferation, but it is unclear how integrin signaling may affect these Cdk2 inhibitors. Here, we demonstrate that integrin ligation led to rapid reduction of p21(CIP1) and p27(KIP1) protein levels in three distinct cell types upon attachment to various extracellular matrix (ECM) proteins, including fibronectin (FN), or to immobilized agonistic anti-integrin monoclonal antibodies. Cell attachment to FN did not rapidly influence p21(CIP1) mRNA levels, while the protein stability of p21(CIP1) was decreased. Importantly, the down-regulation of p21(CIP1) and p27(KIP1) was completely blocked by three distinct proteasome inhibitors, demonstrating that integrin ligation induced proteasomal degradation of these Cdk2 inhibitors. Interestingly, ECM-induced proteasomal proteolysis of a ubiquitination-deficient p21(CIP1) mutant (p21K6R) also occurred, showing that the proteasomal degradation of p21(CIP1) was ubiquitin independent. Concomitant with our finding that the small GTPases Cdc42 and Rac1 were activated by attachment to FN, constitutively active (ca) Cdc42 and ca Rac1 promoted down-regulation of p21(CIP1). However, dominant negative (dn) Cdc42 and dn Rac1 mutants blocked the anchorage-induced degradation of p21(CIP1), suggesting that an integrin-induced Cdc42/Rac1 signaling pathway activates proteasomal degradation of p21(CIP1). Our results indicate that integrin-regulated proteasomal proteolysis might contribute to anchorage-dependent cell cycle control.
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