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Gene & Protein in Disease Bioinformatics study of PCNP

quality factor score. The validation analysis revealed that the I-TASSER-generated structure exhibited the best quality
factor score with maximum amino acids in the favored region. In addition, molecular dynamic simulation analysis
approved the stable structure of the PCNP. This is the first study that highlights the usefulness of the understanding
of the structural and functional analysis of the PCNP, which lays the groundwork for further experimental studies to
validate the outcome.

Keywords: 3D structure; Molecular dynamic simulation; PEST-containing nuclear protein; Phylogeny; Physiochemical
properties; Protein interactions

1. Introduction through MAPK and PI3K/AKT/mTOR signaling pathways
and promoted the apoptosis of neuroblastoma. Meanwhile,
Nuclear proteins (NPs) play a key role in the continuity we also observed opposite results after silencing the PCNP
of cell life by regulating the cell cycle and maintaining the gene in human neuroblastoma cells. These results were
complex organization of the cell . There are various known further strengthened by xenograft tumor analysis in animal
[1]
families of NPs that play very essential roles in various experiments which employed both PCNP overexpression
cellular functions. With unique structure and functions, a and knockdown approaches . Recently, we also revealed
[11]
family of NPs known as PEST-proteins (PEST-NPs), which a novel association of PCNP with the Wnt pathway .
[12]
are rich in proline (P), glutamic acid (E), serine (S), and PCNP is overexpressed in both ovarian cancer tissues and
threonine (T) sequences, acts as signal peptides for protein cells than in para-cancerous tissues and ovarian epithelial
degradation [2,3] . PEST-NPs are also regarded as the guardians cells (IOSE80). Through in vitro and in vivo experiments
of the cell and are believed to play crucial roles in cell cycle on ovarian cancer cells (SK-OV-3 and A2780), it has been
regulation, ubiquitin proteasome pathway, glycosylation found that high expression of PCNP promotes growth,
of nuclear pores, hexosamine biosynthetic pathways, cell migration, and invasion of ovarian cancer cells and
nutrient uptake and cellular metabolism regulation, and inhibits their apoptosis. Furthermore, PCNP could bind
nucleocytoplasmic transport [4-6] . It has been well reported to β-catenin, promote β-catenin nuclear translocation,
that PEST sequences serve as a proteolytic signal to and then activate the Wnt/β-catenin signal pathway .
[12]
degrade the target proteins through proteasome or calpain Based on all these findings, we justify that PCNP can be
proteolysis pathways [7,8] . In 2002, Mori et al. discovered a a promising biomarker for diagnosis and prognosis of
novel PEST-containing nuclear protein (PCNP), which is cancer. Moreover, a potent PCNP inhibitor strategy could
involved in vital cellular processes such as cell proliferation be adopted for exploring PCNP’s role in tumorigenesis.
and mediates tumorigenesis. It is a short-living and small
NP of only 178 amino acids with two remarkable PEST Therefore, it is essential to explore the mechanism
[9]
sequences . Since its discovery, its role has been studied in of PCNP in cancer progression and its applicability as a
several cancers for its relation with cancer progression, and potential target in cancer diagnosis and treatment. To the
now, it is recognized as an oncogenic protein. best of our knowledge, there has been no reported study
on PCNP structure, interactions, and other bioinformatics
PCNP has not been fully explored yet. There are very few analysis related to its evolutionary features as well as
molecular and genomic profiling studies regarding PCNP proteomic profile, and this is the first study to present the
expression in cancer cells. However, in our previous in vitro three-dimensional (3D) structural modeling, interaction
and in vivo studies, we have exploited the tumorigenic roles with other proteins, and physiochemical properties of
of PCNP in neuroblastoma, lungs, and ovarian cancers [10-12] . PCNP. The in silico analysis performed in this study
It has been found that PCNP is upregulated in human demonstrated the features and properties of PCNP
lung adenocarcinoma, and mediates the proliferation, collected from different online web servers and software,
migration, and invasion of cells. However, knockdown which help increase our understanding of PCNP and its
of the PCNP gene is able to reverse the result and retard functions in cellular activities in tumorigenesis.
the progression of adenocarcinoma in the lungs . In
[10]
another study, we evaluated the PCNP gene expression 2. Materials and methods
in neuroblastoma using the SH-SY5Y and SK-N-SH cell
lines. The findings showed that compared to the normal 2.1. Data retrieval and multiple sequence alignment
control group, the high expression of PCNP decreased the The protein ID and FASTA amino acid sequence of PCNP
growth, migration, and invasion of human neuroblastoma were retrieved from the National Center for Biotechnology

Volume 1 Issue 1 (2022) 2 https://doi.org/10.36922/gpd.v1i1.65