skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: NSA2, a novel nucleolus protein regulates cell proliferation and cell cycle

Abstract

NSA2 (Nop seven-associated 2) was previously identified in a high throughput screen of novel human genes associated with cell proliferation, and the NSA2 protein is evolutionarily conserved across different species. In this study, we revealed that NSA2 is broadly expressed in human tissues and cultured cell lines, and located in the nucleolus of the cell. Both of the putative nuclear localization signals (NLSs) of NSA2, also overlapped with nucleolar localization signals (NoLSs), are capable of directing nucleolar accumulation. Moreover, over-expression of the NSA2 protein promoted cell growth in different cell lines and regulated the G1/S transition in the cell cycle. SiRNA silencing of the NSA2 transcript attenuated the cell growth and dramatically blocked the cell cycle in G1/S transition. Our results demonstrated that NSA2 is a nucleolar protein involved in cell proliferation and cell cycle regulation.

Authors:
 [1];  [2];  [1];  [2];  [2];  [3];  [1];  [2];  [1];  [2];  [1];  [2]
  1. Department of Immunology, School of Basic Medical Sciences, Peking University, No. 38 Xueyuan Road, Beijing 100191 (China)
  2. (China)
  3. Chinese National Human Genome Center, Beijing. 3-707 North YongChang Road BDA, Beijing 100176 (China)
Publication Date:
OSTI Identifier:
22199979
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 391; Journal Issue: 1; Other Information: Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL GROWTH; ANIMAL TISSUES; CELL CULTURES; CELL CYCLE; CELL PROLIFERATION; GENE REGULATION; PROTEINS; SIGNALS

Citation Formats

Zhang, Heyu, Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191, Ma, Xi, Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191, State Key Lab of Animal Nutrition, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, Shi, Taiping, Song, Quansheng, Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191, Zhao, Hongshan, E-mail: hongshan@bjmu.edu.cn, Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191, Ma, Dalong, and Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191. NSA2, a novel nucleolus protein regulates cell proliferation and cell cycle. United States: N. p., 2010. Web. doi:10.1016/J.BBRC.2009.11.114.
Zhang, Heyu, Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191, Ma, Xi, Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191, State Key Lab of Animal Nutrition, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, Shi, Taiping, Song, Quansheng, Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191, Zhao, Hongshan, E-mail: hongshan@bjmu.edu.cn, Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191, Ma, Dalong, & Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191. NSA2, a novel nucleolus protein regulates cell proliferation and cell cycle. United States. doi:10.1016/J.BBRC.2009.11.114.
Zhang, Heyu, Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191, Ma, Xi, Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191, State Key Lab of Animal Nutrition, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, Shi, Taiping, Song, Quansheng, Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191, Zhao, Hongshan, E-mail: hongshan@bjmu.edu.cn, Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191, Ma, Dalong, and Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191. 2010. "NSA2, a novel nucleolus protein regulates cell proliferation and cell cycle". United States. doi:10.1016/J.BBRC.2009.11.114.
@article{osti_22199979,
title = {NSA2, a novel nucleolus protein regulates cell proliferation and cell cycle},
author = {Zhang, Heyu and Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191 and Ma, Xi and Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191 and State Key Lab of Animal Nutrition, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193 and Shi, Taiping and Song, Quansheng and Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191 and Zhao, Hongshan, E-mail: hongshan@bjmu.edu.cn and Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191 and Ma, Dalong and Human Disease Genomics Center, Peking University, No. 38 Xueyuan Road, Beijing 100191},
abstractNote = {NSA2 (Nop seven-associated 2) was previously identified in a high throughput screen of novel human genes associated with cell proliferation, and the NSA2 protein is evolutionarily conserved across different species. In this study, we revealed that NSA2 is broadly expressed in human tissues and cultured cell lines, and located in the nucleolus of the cell. Both of the putative nuclear localization signals (NLSs) of NSA2, also overlapped with nucleolar localization signals (NoLSs), are capable of directing nucleolar accumulation. Moreover, over-expression of the NSA2 protein promoted cell growth in different cell lines and regulated the G1/S transition in the cell cycle. SiRNA silencing of the NSA2 transcript attenuated the cell growth and dramatically blocked the cell cycle in G1/S transition. Our results demonstrated that NSA2 is a nucleolar protein involved in cell proliferation and cell cycle regulation.},
doi = {10.1016/J.BBRC.2009.11.114},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 391,
place = {United States},
year = 2010,
month = 1
}
  • Histatins are salivary proteins with antimicrobial activities. We previously reported that histatin 3 binds to heat shock cognate protein 70 (HSC70), which is constitutively expressed, and induces DNA synthesis stimulation and promotes human gingival fibroblast (HGF) survival. However, the underlying mechanisms of histatin 3 remain largely unknown. Here, we found that the KRHH sequence of histatin 3 at the amino acid positions 5–8 was essential for enhancing p27{sup Kip1} (a cyclin-dependent kinase inhibitor) binding to HSC70 that occurred in a dose-dependent manner; histatin 3 enhanced the binding between p27{sup Kip1} and HSC70 during the G{sub 1}/S transition of HGFs asmore » opposed to histatin 3-M(5–8) (substitution of KRHH for EEDD in histatin 3). Histatin 3, but not histatin 3-M(5–8), stimulated DNA synthesis and promoted HGF survival. Histatin 3 dose-dependently enhanced both p27{sup Kip1} and HSC70 ubiquitination, whereas histatin 3-M(5–8) did not. These findings provide further evidence that histatin 3 may be involved in the regulation of cell proliferation, particularly during G{sub 1}/S transition, via the ubiquitin–proteasome system of p27{sup Kip1} and HSC70. - Highlights: • KRHH amino acid sequence was required in histatin 3 to bind HSC70. • Histatin 3 enhanced HSC70 binding to p27{sup Kip1} during the G{sub 1}/S transition in HGFs. • KRHH sequence stimulated DNA synthesis and promoted cell survival. • Histatin 3 dose-dependently enhanced both p27{sup Kip1} and HSC70 ubiquitination. • Histatin 3 stimulates cell proliferation via the ubiquitin–proteasome system.« less
  • Highlights: Black-Right-Pointing-Pointer Tumor suppressive microRNA-133a regulates moesin (MSN) expression in HNSCC. Black-Right-Pointing-Pointer Silencing of MSN in HNSCC cells suppressed proliferation, migration and invasion. Black-Right-Pointing-Pointer The expression level of MSN was significantly up-regulated in cancer tissues. -- Abstract: Recently, many studies suggest that microRNAs (miRNAs) contribute to the development, invasion and metastasis of various types of human cancers. Our recent study revealed that expression of microRNA-133a (miR-133a) was significantly reduced in head and neck squamous cell carcinoma (HNSCC) and that restoration of miR-133a inhibited cell proliferation, migration and invasion in HNSCC cell lines, suggesting that miR-133a function as a tumor suppressor.more » Genome-wide gene expression analysis of miR-133a transfectants and TargetScan database showed that moesin (MSN) was a promising candidate of miR-133a target gene. MSN is a member of the ERM (ezrin, radixin and moesin) protein family and ERM function as cross-linkers between plasma membrane and actin-based cytoskeleton. The functions of MSN in cancers are controversial in previous reports. In this study, we focused on MSN and investigated whether MSN was regulated by tumor suppressive miR-133a and contributed to HNSCC oncogenesis. Restoration of miR-133a in HNSCC cell lines (FaDu, HSC3, IMC-3 and SAS) suppressed the MSN expression both in mRNA and protein level. Silencing study of MSN in HNSCC cell lines demonstrated significant inhibitions of cell proliferation, migration and invasion activities in si-MSN transfectants. In clinical specimen with HNSCC, the expression level of MSN was significantly up-regulated in cancer tissues compared to adjacent non-cancerous tissues. These data suggest that MSN may function as oncogene and is regulated by tumor suppressive miR-133a. Our analysis data of novel tumor-suppressive miR-133a-mediated cancer pathways could provide new insights into the potential mechanisms of HNSCC oncogenesis.« less
  • A Gtr1p GTPase, the GDP mutant of which suppresses both temperature-sensitive mutants of Saccharomyces cerevisiae RanGEF/Prp20p and RanGAP/Rna1p, was presently found to interact with Yrb2p, the S. cerevisiae homologue of mammalian Ran-binding protein 3. Gtr1p bound the Ran-binding domain of Yrb2p. In contrast, Gtr2p, a partner of Gtr1p, did not bind Yrb2p, although it bound Gtr1p. A triple mutant: yrb2{delta} gtr1{delta} gtr2{delta} was lethal, while a double mutant: gtr1{delta} gtr2{delta} survived well, indicating that Yrb2p protected cells from the killing effect of gtr1{delta} gtr2{delta}. Recombinant Gtr1p and Gtr2p were purified as a complex from Escherichia coli. The resulting Gtr1p-Gtr2p complexmore » was comprised of an equal amount of Gtr1p and Gtr2p, which inhibited the Rna1p/Yrb2 dependent RanGAP activity. Thus, the Gtr1p-Gtr2p cycle was suggested to regulate the Ran cycle through Yrb2p.« less
  • Highlights: {yields} Loss of MUC4 reduces proliferation of esophageal cancer cells. {yields} MUC4 inhibition impairs migration of esophageal cancer cells but not their invasion. {yields} Loss of MUC4 significantly reduces in vivo tumor growth. {yields} Decrease of S100A4 induced by MUC4 inhibition impairs proliferation and migration. -- Abstract: MUC4 is a membrane-bound mucin known to participate in tumor progression. It has been shown that MUC4 pattern of expression is modified during esophageal carcinogenesis, with a progressive increase from metaplastic lesions to adenocarcinoma. The principal cause of development of esophageal adenocarcinoma is the gastro-esophageal reflux, and MUC4 was previously shown tomore » be upregulated by several bile acids present in reflux. In this report, our aim was thus to determine whether MUC4 plays a role in biological properties of human esophageal cancer cells. For that stable MUC4-deficient cancer cell lines (shMUC4 cells) were established using a shRNA approach. In vitro (proliferation, migration and invasion) and in vivo (tumor growth following subcutaneous xenografts in SCID mice) biological properties of shMUC4 cells were analyzed. Our results show that shMUC4 cells were less proliferative, had decreased migration properties and did not express S100A4 protein when compared with MUC4 expressing cells. Absence of MUC4 did not impair shMUC4 invasiveness. Subcutaneous xenografts showed a significant decrease in tumor size when cells did not express MUC4. Altogether, these data indicate that MUC4 plays a key role in proliferative and migrating properties of esophageal cancer cells as well as is a tumor growth promoter. MUC4 mucin appears thus as a good therapeutic target to slow-down esophageal tumor progression.« less
  • Highlights: Black-Right-Pointing-Pointer Mxi1 regulates cell proliferation. Black-Right-Pointing-Pointer Expression of IGFBP-3 is regulated by Mxi1. Black-Right-Pointing-Pointer Inactivation of Mxi1 reduces IGFBP-3 expression in vitro and in vivo. -- Abstract: Mxi1, a member of the Myc-Max-Mad network, is an antagonist of the c-Myc oncogene and is associated with excessive cell proliferation. Abnormal cell proliferation and tumorigenesis are observed in organs of Mxi1-/- mice. However, the Mxi1-reltaed mechanism of proliferation is unclear. The present study utilized microarray analysis using Mxi1 mouse embryonic fibroblasts (MEFs) to identify genes associated with cell proliferation. Among these genes, insulin-like growth factor binding protein-3 (IGFBP-3) was selected asmore » a candidate gene for real-time PCR to ascertain whether IGFBP-3 expression is regulated by Mxi1. Expression of IGFBP-3 was decreased in Mxi1-/- MEFs and Mxi1-/- mice, and the gene was regulated by Mxi1 in Mxi1 MEFs. Furthermore, proliferation pathways related to IGFBP-3 were regulated in Mxi1-/- mice compared to Mxi1+/+ mice. To determine the effect of Mxi1 inactivation on the induction of cell proliferation, a proliferation assay is performed in both Mxi1 MEFs and Mxi1 mice. Cell viability was regulated by Mxi1 in Mxi1 MEFs and number of PCNA-positive cells was increased in Mxi1-/- mice compared to Mxi1+/+ mice. Moreover, the IGFBP-3 level was decreased in proliferation defect regions in Mxi1-/- mice. The results support the suggestion that inactivation of Mxi1 has a positive effect on cell proliferation by down-regulating IGFBP-3.« less