Inhibition of angiogenesis by the BTB domain of promyelocytic leukemia zinc finger protein

Rho, Seung Bae; Choi, Kyusam; Park, Kyoungsook; Lee, Je-Ho

doi:10.1016/j.canlet.2010.01.021

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Volume 294, Issue 1 , Pages 49-56, 1 August 2010

Inhibition of angiogenesis by the BTB domain of promyelocytic leukemia zinc finger protein

Seung Bae Rho
- Research Institute, National Cancer Center, 323, Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, Republic of Korea
- Corresponding author. Tel.: +82 31 920 2383; fax: +82 31 920 2399.
Kyusam Choi
- Molecular Therapy Research Center, Sungkyunkwan University, B4-193 Cancer Center, Samsung Medical Center, 50, Irwon-dong, Kangnam-gu, Seoul 135-710, Republic of Korea
- College of Science and Technology, Division of Biological Science and Technology, Yonsei University, Wonju, Gangwon-do 220-710, Republic of Korea
Kyoungsook Park
- Molecular Therapy Research Center, Sungkyunkwan University, B4-193 Cancer Center, Samsung Medical Center, 50, Irwon-dong, Kangnam-gu, Seoul 135-710, Republic of Korea
Je-Ho Lee
- Molecular Therapy Research Center, Sungkyunkwan University, B4-193 Cancer Center, Samsung Medical Center, 50, Irwon-dong, Kangnam-gu, Seoul 135-710, Republic of Korea
- Division of Gynecologic Oncology, Department of Obstertrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Irwondong, Kangnam-gu, Seoul 135-710, Republic of Korea

Received 15 July 2008; received in revised form 19 January 2010; accepted 20 January 2010. published online 18 March 2010.

Abstract

Promyelocytic leukemia zinc finger is a negative regulator of cell cycle progression. In this study, we showed that PLZF inhibits endothelial cell angiogenesis using a human umbilical vein endothelial cell system. We also focused on characterizing the specific function of the BTB domain of PLZF as a novel apoptotic and anti-angiogenic protein via deletion mapping analysis. The BTB domain directly inhibited tube formation, as well as the biological functions of angiostatic activity in vivo, and reduced the expression of p-Akt and p-eNOS, which play a significant role in angiogenesis when stimulated by VEGF. These results strongly suggest that the BTB domain could potentially modulate the apoptotic and anti-angiogenic effects of PLZF.

Abbreviations: PLZF, promyelocytic leukemia zinc finger, HUVEC, human umbilical vein endothelial cell, VEGF, vascular endothelial growth factor, CAM, chick chorioallantoic membrane

Keywords: Angiogenesis, BTB/POZ domain, Crystal-based structure, Anti-angiogenic protein, Therapeutic target