''Reprimo'' (RPRM), is a

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

located at human chromosome 2q23 whose expression in conjunction with

p53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...

, along with other genes which are p53-induced, is associated with the arrest of the

cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...

at the

G2 phase G2 phase, Gap 2 phase, or Growth 2 phase, is the third subphase of interphase in the cell cycle directly preceding mitosis. It follows the successful completion of S phase, during which the cell’s DNA is replicated. G2 phase ends with the o ...

. ''Reprimo's'' protein product is a highly

glycosylated Glycosylation is the reaction in which a carbohydrate (or 'glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not alw ...

polypeptide which, upon its expression, is localized to the

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...

where it is primarily active. As the expression of ''reprimo'' is controlled by p53, which is in turn controlled by a wide array of convergent signal pathways pertaining to DNA damage or nutrient depravity, its presence is expected within cells which would cause damage should they be freely allowed to replicate. Pursuant to this, r''eprimo'''s expression during the G2 phase of the cell cycle ultimately results in the reduction of

Cdc2 Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in th ...

expression, and in the inhibition of the nuclear translocation of

cyclin B1 G2/mitotic-specific cyclin-B1 is a protein that in humans is encoded by the ''CCNB1'' gene. Function Cyclin B1 is a regulatory protein involved in mitosis. The gene product complexes with p34 (Cdk1) to form the maturation-promoting factor (MPF) ...

which is necessary to its function. ''Reprimo'' is known to collaborate with

p21 p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, though is primarily associated ...

to achieve these specific effects, and in a more general sense collaborates with the other p53-induced proteins and effectors to produce the overall cellular response. These regulatory actions help to render the afflicted cell into an arrested state which is less immediately threatening to the whole organism due to the inability of afflicted cells to replicate with damaged DNA, among other potential circumstances, giving the cell an opportunity to undergo

DNA repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dam ...

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

as the level of damage will dictate. Indefinite cell cycle arrest is another potential outcome. For this reason, it is considered to be a

tumor suppressor gene A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or red ...

. Identification of this gene's repression via

methylation In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These t ...

to its upstream promoter region within various types of

cancerous Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Poss ...

tissue have been used to suggest a connection to the formation of said cancer. These methylation events commonly cause aberrant DNA splicing which may cause one of many potential errors within the resulting

mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...

''reprimo'' that ultimately undermine its ability to be expressed, have its intended effects, or to accumulate in sufficient quantities to produce the expected arrest reaction. The variability of these outcomes is owed to the large

probability space In probability theory, a probability space or a probability triple (\Omega, \mathcal, P) is a mathematical construct that provides a formal model of a random process or "experiment". For example, one can define a probability space which models t ...

for these point mutations. There is also research to suggest that this gene's expression status within specific tissues may be useful information for the diagnosis or prognosis of certain types of cancer.

Utility in cancer detection and prognosis

Given ''reprimo'''s inherent role in cancer prevention, investigations have focused on whether it is a point of failure worth monitoring for the purposes of diagnosis. In contrast to non-

malignant Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...

tissues, in which it has been found in less than eleven percent of samples, methylations to ''reprimo'''s promoter region have been detected in a majority of gastric, gallbladder, lymphoma, and colorectal cancers, and in significant proportions of esophageal adenocarcinomas, breast cancers and leukemias. In other types of cancer, the presence of these methylations are not significantly more common than the baseline non-cancerous tissues. In those whom have already been diagnosed with primary pancreatic cancer, there is a correlative relationship to suggest there will be a much worse prognosis when said tissues were found to contain these methylations to ''reprimo'''s promoter. In terms of early detection, the methylation status of ''reprimo'' in esophageal and gastric tissues have had some success in predicting the development of cancer. In the case of gastric cancer, detection methods include sampling of blood plasma.

References

{{reflist Genes on human chromosome 2