Identification of nuclear localization signal that governs nuclear import of BRD7 and its essential roles in inhibiting cell cycle progression - PubMed (original) (raw)

. 2006 Jul 1;98(4):920-30.

doi: 10.1002/jcb.20788.

Huaying Liu, Xiaojie Xu, Houde Zhou, Xiaoling Li, Cong Peng, Shourong Shen, Wei Xiong, Jian Ma, Zhaoyang Zeng, Songqing Fang, Xinmin Nie, Yixin Yang, Jie Zhou, Juanjuan Xiang, Li Cao, Shuping Peng, Shufang Li, Guiyuan Li

Affiliations

Identification of nuclear localization signal that governs nuclear import of BRD7 and its essential roles in inhibiting cell cycle progression

Ming Zhou et al. J Cell Biochem. 2006.

Abstract

BRD7, a novel bromodomain gene, is identified to be associated with nasopharyngeal carcinoma (NPC). Decreased or loss of expression of BRD7 was detected in NPC biopsies and cell lines. Overexpression of BRD7 could inhibit NPC cell growth and arrest cells in cell cycle by transcriptionally regulating some important molecules involved in ras/MEK/ERK and Rb/E2F pathway, and downregulate the promoter activity of E2F3. In the present study, the subcellular localization of BRD7 was investigated. It was found that BRD7 was mainly localized in nucleus without distinct cell-specific difference between COS7 and HNE1. Furthermore, a functional nuclear localization signal (NLS) sequence ranging from amino acid 65 to 96 was identified and characterized. The NLS is composed of a cluster of four bipartite nuclear targeting sequences, which are tightly linked and extremely overlapped. We found that whether the entire NLS or the four bipartite nuclear targeting sequences could respectively determine the nuclear import of green fluorescent protein (GFP). The most important is that NLS-deleted BRD7 shifted the nuclear localization to be mostly in cytoplasm, and failed or reduced to negatively regulate the expression of cell cycle related molecules, cyclin D1 and E2F3, and cell cycle progression from G1 to S phase. In conclusion, NLS is an essential motif affecting BRD7 nuclear distribution, and the nuclear localization of BRD7 is critical for the expression of cell cycle related molecules and cell biological function.

2006 Wiley-Liss, Inc.

PubMed Disclaimer

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources