Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Sep;32(9):e126-34.
doi: 10.1161/ATVBAHA.112.247502. Epub 2012 Jun 28.

Heat shock cognate 70 regulates the translocation and angiogenic function of nucleolin

Yanping Ding  1 , Nan Song, Chang Liu, Ting He, Wei Zhuo, Xiaoli He, Yang Chen, Xiaomin Song, Yan Fu, Yongzhang Luo
Affiliations

Heat shock cognate 70 regulates the translocation and angiogenic function of nucleolin

Yanping Ding et al. Arterioscler Thromb Vasc Biol. 2012 Sep.

Abstract

Objective: Cell surface nucleolin (NCL) plays fundamental roles in tumor angiogenesis. However, the mechanism underlying its surface translocation remains obscure. The present study discovered that heat shock cognate 70 (Hsc70) is essential in both the surface translocation and the angiogenic function of NCL.

Methods and results: We identified that Hsc70 interacted with NCL in endothelial cells via the peptide-binding domain of Hsc70 and the RNA-binding domain of NCL. Functional knockdown of Hsc70 remarkably inhibited the expression of surface NCL, which was rescued by wild-type Hsc70 rather than its truncations. Phosphorylation of NCL by either protein kinase C-ξ or casein kinase 2 mediated its interaction with Hsc70 and the surface expression. Hsc70 regulated NCL translocation via stabilizing NCL and enhancing its interaction with nonmuscle myosin heavy chain 9. Moreover, Hsc70 was associated with NCL-induced endothelial cell migration and tubule formation in vitro and angiogenesis in both matrigel plugs and xenograft tumors. Tissue array analysis revealed that the expression levels of NCL and Hsc70 were intimately correlated in human lung adenocarcinomas.

Conclusions: Our study demonstrates that Hsc70 is a prerequisite for the surface translocation and angiogenic function of NCL, which suggests strategies to target both Hsc70 and NCL for more effective antiangiogenic therapies.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources