Cytosolic p21Waf1/Cip1 increases cell cycle transit in vascular smooth muscle cells

Yao Dong, Sylvia L. Chi, Alexander D Borowsky, Yaping Fan, Robert H Weiss

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

The intracellular localization of signaling proteins is critical in directing their interactions with both upstream and downstream signaling cascade components. While initially described as a cyclin kinase inhibitor, p21Waf1/Cip1 has since been shown to have bimodal effects on cell cycle progression and cell proliferation, and evidence is emerging that intracellular localization of this protein plays a role in directing its signaling properties by dictating its interactions with downstream molecules. Since we have previously demonstrated a pro-apoptotic and cell cycle inhibitory effect of p21 attenuation after transfection of antisense p21 oligodeoxynucleotides (ODN) in several cell lines, we asked whether cytosolic p21 mediates a positive effect on vascular smooth muscle (VSM) cell cycle transit. We now show that transfection of a nuclear-localization signal deficient (ΔNLS) p21 construct into VSM cells results in increased cytosolic levels of p21 and causes increased cell cycle transit as measured by [3H]thymidine incorporation. Thus, at least in VSM cells, cytosolic localization of p21 is a means by which this signaling protein transmits pro-mitogenic signals to the proteins responsible for G1/S transition. Furthermore, compartmentalization of p21 may help explain the biphasic nature of p21 in a variety of cell types and may lead to therapeutic advances directed at modulating pathologic cell growth in vascular diseases and cancer.

Original languageEnglish (US)
Pages (from-to)263-269
Number of pages7
JournalCellular Signalling
Volume16
Issue number2
DOIs
StatePublished - Feb 2004

Keywords

  • Nuclear-localization signal
  • Oligodeoxynucleotides
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Cell Biology

Fingerprint

Dive into the research topics of 'Cytosolic p21<sup>Waf1/Cip1</sup> increases cell cycle transit in vascular smooth muscle cells'. Together they form a unique fingerprint.

Cite this