Roles of NUCKS1 in Diseases: Susceptibility, Potential Biomarker, and Regulatory Mechanisms.

Pengru Huang,Yujie Cai,Bin Zhao,Lili Cui

doi:10.1155/2018/7969068

Abstract

Nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) is a 27 kD chromosomal, highly conserved, and vertebrate-specific protein. NUCKS1 gene encodes a nuclear protein and the conserved regions of NUCKS1 contain several consensus phosphorylation sites for casein kinase II (CK2) and cyclin-dependent kinases (Cdk) and a basic DNA-binding domain. NUCKS1 is similar to the high mobility group (HMG) family which dominates chromatin remodeling and regulates gene transcription. Meanwhile, NUCKS1 is a RAD51 associated protein 1 (RAD51AP1) paralog that is significant for homologous recombination (HR) and genome stability and also a transcriptional regulator of the insulin signaling components. NUCKS1 plays an important role in DNA damage response and metabolism, participates in inflammatory immune response, and correlates with microRNA. Although there is still not enough functional information on NUCKS1, evidences suggest that NUCKS1 can be used as the biomarker of several cancers. This review summarizes the latest research on NUCKS1 about its susceptibility in diseases, expression levels, and regulatory mechanisms as well as the possible functions in reference to diseases.

Highlights

Nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1), which is located on human chromosome 1q32.1 [1], is a member of the high mobility group (HMG) family [2]; NUCKS1 is widespread in vertebrates and is expressed ubiquitously by almost all human cell types [2,3,4]
The exact roles of NUCKS1 in diseases remain obscure, it has been reported that expression and transcription levels of NUCKS1 are significantly associated with Parkinson disease (PD) [13, 22] and that NUCKS1 transcription and methylation are likely to play a vital role in youths with bipolar disorder (BD) [30]
NUCKS1 may be associated with a selective advantage during tumor initiation and development that allows early neoplastic cells to overcome replication stress [47]

Summary

Introduction

Nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1), which is located on human chromosome 1q32.1 [1], is a member of the high mobility group (HMG) family [2]; NUCKS1 is widespread in vertebrates and is expressed ubiquitously by almost all human cell types [2,3,4]. In contrast to HMG, NUCKS1 is highly phosphorylated at multiple sites [5, 6]. NUCKS1 can be phosphorylated by kinases, such as casein kinase II (CK2) and cyclindependent kinase (Cdk) and DNA-activated protein kinase. In vitro experiments have indicated that NUCKS1 can act as a substrate for second messenger-activated kinases [11]. The aforementioned functions of NUCKS1 contribute to the susceptibility, occurrence, and development of several cancers and other diseases and suggest that NUCKS1 could be a potent marker for such diseases [12]. An understanding of additional potential functions of NUCKS1 may provide new insight into novel therapeutic strategies to address the development of these diseases. We focus on new evidence regarding the associations between NUCKS1 and susceptibility to diseases; NUCKS1 expression levels in diseases; and regulatory mechanisms involving NUCKS1 in the context of diseases

Genetic Susceptibilities Associated with NUCKS1

Levels of NUCKS1 in Diseases

Functions of NUCKS1 in Diseases

Findings

Conclusions and Perspectives