IS POPDC 1 A POTENTIAL TREATMENT TARGET IN MULTIPLE CANCERS?.

IS POPDC 1 A POTENTIAL TREATMENT TARGET IN MULTIPLE
CANCERS?
1

Table of contents
Table of Contents
INTRODUCTION.......................................................................................................................................................... 3
DISCUSSION:................................................................................................................................................................. 3
IDEAS AND STATE OF THE FIELD.................................................................................................................................... 3
A) CONCEPT OF POPEYE GENE FAMILY.................................................................................................................... 3
B) STRUCTURE OF POPEYE PROTEINS...................................................................................................................... 4
C) POPEYE DOMAIN AS THE CAMP BINDING DOMAIN FOR TARGETING.........................................................................6
D) INVOLVEMENT AND EXPRESSION AND THE PATTERN OF POPDC GENES....................................................................7
E) THE BEHAVIOUR OF POPEYE PROTEIN AND MECHANISM OF POPDC IN SIGNALLING CANCER.....................................8
F) EVIDENCE COLLECTED FROM THE LITERATURE......................................................................................................... 10
G) INTEGRATING INFORMATION TO RESEARCH QUESTIONS........................................................................................11
H) SUGGESTION FOR EGFR EXPRESSION IN DOWN REGULATIONS IN CANCEROUS CELL................................................11
CONCLUSION.............................................................................................................................................................. 12
LITERATURE GAP:........................................................................................................................................................ 13
THE FUTURE DIRECTION OF RESEARCH:....................................................................................................................... 13
REFERENCE LIST.......................................................................................................................................................... 14
2

Introduction
The Popeye domain comprises of the POPDC proteins which are regulated
by the POPDC gene. These are expressed in several tissues as well as cell
types and are present in sub cellular compartments and they interact with
various protein classes. These POPDC proteins combine with cAMP with
strong affi nity. This topic aims to research the pattern, expression, and role
of POPDC proteins in breast and other cancers such as gastric cancer,
colorectal cancer, and hepato-cellular carcinoma. Moreover, targeting of
this protein and different aspects of down-regulation of the proteins are to
be discussed. This is important because the protein family can function in
several tissues and they act as a potential and significant therapeutic
target in cancer.
The scope of this study considers that over expression of the POPDC
proteins reduces migration of cancer cells along with in vitro invasion. This
protein acts as a promising therapeutic target for treating cancer. Hence,
this specific topic focuses on identification of the POPDC proteins involved
in malignant processes in breast cancer along with considering viability as
a drug target for cancer treatment.
Ideas and state of the field
a) Concept of Popeye Gene family
According to Brand (2018), the POPDCgene family consists of 3 genes named POPDC1,
POPDC2 and POPDC3. As stated by Lin et al. (2018), the POP proteins encoded by the
POPDC gene comprise of three putative transmembrane domains. In the human genome,
these are situated at chromosome 6q21. The POPDC2 gene is situated upon chromosome
3q13.33. The POPDC 1 gene is considered as the most complex with 8 exons.
b) Structure of Popeye proteins
According to Brand (2018), POPDC proteins are medium-sized transmembrane proteins.
These involve a short extracellular domain (ECD) which is subjected to N-glycosylation.
Three transmembrane domains are present in POPDC protein. In the cytoplasmic part, a
3

conserved Popeye domain of is present that functions as the motif for cAMP to bind. This
Popeye domain is larger compared to basic cyclic nucleotide monophosphate or cGMP
binding domain and suggests additional functions for the Popeye domain. The structure of
the Popeye domain is 20-40 amino acids in length and the extracellular part of the
transmembrane comprises the sites of N-glycosylation. The cytoplasmic part of POPDC
includes a CTD or carboxy-terminal domain and Popeye domain. The glycosylation property
affects the electrophoretic mobility during the SDS PAGE experiment. In SDS PAGE,
POPDC runsat58 kDa while the protein is predicted with the molecular weight of 42 kDa.
However, this glycosylation varies across tissues. The impact of glycosylation is not known
currently; nevertheless, this has been hypothesized to play a vital role in membrane
localization of these POPDC proteins.
Figure 1: structure of POP Protein OPDC protein (Source: Brand, 2018)
Soon after the discovery of POPDC1, dimerisation behaviour was detected. This dimerisation is
stabilized by the formation of a di-sulfide bridge. The mapping of the dimeric sequences was studied
with the help of molecular experiments. These include deletion of a carboxy-terminal part, mapping of
peptides and mutagenesis that are site-directed.
4