Viola Romm-Troddle,A Jeff Vader,B Archipelago JonesA and Günther SchlonkC*
Abstract: The protein “putin” normally acts to regulate the flow of methane through the digestive system. However, a nonsense mutation of the corresponding KGB gene results in an antimorphic protein, “RASputin” which is linked to a highly invasive cancer known as russocarcinoma. X-ray crystallomancy and detailed reactivity studies have revealed how Reactive Aggressive Species are formed at tsarine residues in the reactionary sites of RASputin, and go on to seize the means of reaction within affected cells. The resultant tumorigenic activity is presaged by a build-up of T-72/90 lysosomes at the cell wall, followed by a rapid and simultaneous incursion into neighbouring cells. Early treatment models include infusions of macrophages and restricting blood flow to the affected area.
Russocarcinoma has been known since ancient times, and by various names. To the ancient Greeks, it was asthenopyge, to the Romans: fuscus infirmium posterius, and to the Germans as Furzschattenkrankensterben. Today it is classified as a form of aggressive colorectal cancer. Only recently have the biochemical underpinnings of this cruel and crippling disease been uncovered. This incomprehensive illiterature review aims to summarise the discovery, genetic origins and treatment of russocarcinoma, and the role that the putin protein plays in its development.
1. The KGB gene and its mutation
The first step on the path to understanding russocarcinoma was the observation that the disease appeared to be heritable. Geneticists W. Heel and B. Beestinger conducted a 1969 case study of cancer patients in Vladivostok, which uncovered several unusual pedigrees (figure 1).1
While compelling, this evidence was initially overlooked by many due to confounding factors present within the families examined. It was not until 1992 that linkage studies led to identification of the associated gene and causative mutation. This gene bears the names of its discoverers, and is known as the Khrushchev-Gorbachev-Brezhnev (KGB) gene.2 Further insight into the nature of the KGB gene and its mutation were provided by N. Romanov and co-workers in 1999.3 The gene is located on chromosome 17, and comprises 146,038,899 base pairs over 85 exons. the variant linked to RC is a frame-shift mutation that causes collectivisation and redistribution of all 85 exons, resulting in premature chain termination and non-sense mediated decay. The sequence of KGB and its variant can be found on the OBLAST database.4 As a result of this study the KGB variant was designated as class 5: pathogenic. A more recent study led by the Yeltsin group at Smirnoff University found that this mutation could be induced in vitro simply by exposing cells to a 40% solution of ethanol.5
2. Putin’s Structure and Reactivity
Amélie du Pomme de Terre was responsible for first studying the protein encoded by the KGB gene. In 1995, she identified a globular intestinal protein as that encoded by KGB, and studied its role in transporting methane and other natural gasses through the digestive system. She had intended to name it “putain” as a reference to its promiscuous gas-binding, but because of an auto-correct error, it was published as “putin” and the name stuck.6 Putin is atypical of proteins; in that it contains two unusual amino acids: lenine and tsarine (figure 2). In wildtype putin, the lipophilic nature of lenine residues bind non-polar gasses like CH4, while tsarine forms hydrogen bonds with NH3 and SH2.
A landmark study by M. Boney uncovered the mechanism by which the mutated putin protein causes cancer.7 A series of painstaking and intricate experiments far too complex to describe8 revealed that reactive aggressive species (RAS) were being generated by putin, and were responsible for damaging cellular DNA. These compounds are highly energetic radicals such as F•, Cl•, RP(O)O•, OH• and FOOF•. They are formed via some poorly defined radical unga-bunga, and are capable of slipping through the membranes of various organelles. Once inside, these radicals cause havoc with the cellular machinery, effectively seizing the means of reaction within the cell. When the nucleus is compromised by these radicals, the life cycle of the cell is drastically altered, leading to rapid, uncontrolled proliferation. The effects of RAS on nitrogenous biomolecules are comprehensively reviewed in Vitas’s paper on the 7th element.9 On account of these species, the mutant form of putin is often referred to as RASputin.
In 2018, a group of researchers at Stolichnaya university succeeded in crystalising RASputin.10 The resulting X-ray crystallomancy data was invaluable in the elucidation of RASputin’s tertiary and quaternary structure (figure 3).
Regarding the overall structure, two main domains are distinguishable. The first is an elongated barrel-shaped protuberance with a porous end-cap, and the second is a pair of globular units at one end. Each globular unit contains a reactionary site, responsible for the generation of radically aggressive species. These sites each contain multiple tsarine residues, which are the ultimate source of the RAS. The elongated domain is an alpha-helical barrel, commonly referred to as an alpha complex. RAS pass down the barrel from the reactionary sites and out into the cell through the end-cap. The outer surface of the protein is rich in lenine residues, which are responsible for its greasy nature and affinity of cell membranes. The interior structure is maintained by bi-polar interactions.
NMR spectroscopy has also been used to probe the dynamic nature of RASputin in solution. A notable study by Otter and Sax used Transverse Relaxation-Optimised Thermal Spectro-CryoscopY (TROTSCY) to investigate the relationship between temperature and structure in RASputin.10½ They observed a marked contraction of both the alpha complex and the globular masses at lower temperature. This shrinkage was reversed when the sample was warmed back up. Further studies encompassing docking and host/guest interactions are ongoing, and should prove fascinating.
A previously overlooked component of RASputin’s structure was its glycosylation: RASputin bears a tetrasaccharide known as fucnose (figure 4). This sugar consists of a ribose-arabinose-ribose-arabinose sequence and belongs to the family of oligarchosaccharides. Hence, the protein is sometimes referred to as RARA-RASputin, or Fuc-RASputin. The role of this glycan is not clear, but it may help RASputin evade proteasomes.
Russocarcinoma has two distinct stages. The first is a dormant stage, lasting up to eight years. During this time, the disease leaves no outwardly obvious signs. On cellular level, however, stage one is characterised by a build-up of type-72 and type-90 lysosomes in pockets near the cell wall (figure 5).
Stage II begins with a rapid, synchronised incursion by these lysosomes into neighbouring cells. These rogue lysosomes are highly destructive, and the resulting DNA degradation prompts the neighbouring cell to malfunction in like manner. This process rapidly results in a metastatic, highly invasive cancer. Benedict Kranksnorkel has reported abnormal hormonal activity originating from russocarcinomas.11 He proposes that the resulting imbalances in the endocrine system may be responsible for the altered emotional behaviour associated with RC. Kranksnorkel identifies four main hormones whose levels are directly affected by RASputin (figure 6).
An excess of fanatic acid is known to promote violent mood swings, irrational and aggressive behaviour, while dneipamine deficiency can cause tunnel vision and a lack of spatial awareness. Mariutonin insufficiency is strongly correlated with psychosis. Pravdasterone, on the other hand, can cause premature balding in males.
The treatment of russocarcinoma is inherently difficult, like any aggressive cancer. Scientists in Germany and Poland have trialled an infusion of macrophages to help the body fight off the cancer. Alternatively, a research group in the US suggests restricting blood flow to the affected area, to deprive the tumour of the nutrients essential for further growth, though this can lead to necrosis of the surrounding tissue and further complications. Regardless of type of treatment available, sufferers should remain resolute in the face of this grotesque malignancy. Those afflicted with russocarcinoma should know that they are not alone, and that people all over the world stand with them, in whatever ways they can.
Russocarcinoma is a malignant and invasive cancer, caused by a senseless mutation in the KGB gene. The result of this mutation is the pathogenic RASputin protein, which generates reactive aggressive species and causes catastrophic damage to cellular DNA. Current treatments target symptoms, and more research is desperately needed to treat the root cause.
V. R-T. prepared figure 1 and assisted in the preparation of the manuscript. G. S. prepared the manuscript. A. J. gave a favourable beer-review in exchange for authorship. J. V. provided the snacks.
About the Authors
“Nitwit, blubber, oddment, tweak!” – Viola Rom-Troddle
Archipelago Jones has led the Gregor Mendacity Institute for Genetics for twenty years, during which time she helped to discover chromosome 27. Jeff Vader is head of catering. Demeritus Professor Günther Schlonk heads the Department of Pyrofrolics and Inorganometallics at the University of West Failure, and is Imperial Editor in Perpetuity of The Journal of Immaterial Science. At 13, he was diagnosed with a pathological inability to take things seriously, a condition that still gets him into trouble today. He recently fell ill after eating a bar of Novichocolate® at a conference in Omsk.
The authors declare that the contents of this paper are 100% verifiable bullshit. The authors do not intend to make light of cancer or the current events in Europe, nor to deride any nationality or people. Our goal is simply to take the piss out of one despot in particular. Just in case that wasn’t clear.
The authors also declare that they have never been photographed shirtless on a horse. Never.
Conflicts of Interest
Günther Schlonk is not a molecular biologist, an oncologist nor a geneticist, and this article should have made that blatantly obvious.
Notes and references
1 W. Heel, B. Beestinger, 1969, J. Generic Counselling. 4, 456–457.
2 N. S. Krushchev, M. S. Gorbachev, L. I. Brezhnev, 1992, Cell N. Stuff. 1, 123–456.
3 A. Feodorovna, N. Romanov, 1999, Russ. Imp. J. Biochem. II, 1868–1917.
4 OBLAST database: https://blast.ncbi.nlm.nih.gov/Blast.cgi
5 B. Yeltsin, 2017, J. Self Med. Chem. 8, 1991–1999
6 A. P. Terre, 2003, PLUS One, 1, 2–3.
7 M. Boney et al. 2005 J. Mus. Chem. 2, 1–234.
8 Don’t you wish you could write this in a real paper?
9 Vitas et al. 2006, J. Mus. Chem. 7, 878–879.
10 S. Putnik, V. Ushanka, I. Valenki, 2018, Izvestia, 17, 1905–1917.
10½ G. Otter, A. Sax, 2019, J. Am. Chem. Socks. 2542, 385434.-385489.
11 B. Kranksnorkel, T. G. Katherine, 2019, Russ. Ortho. J. Chem. 13, 65–72.
TMITPOTC The Mitochondria Is The Powerhouse Of The Cell
TLDR Too long Didn’t Read
HGESGXGNSJXDNLELM See Above
WITAEF What Is This Abbreviation Even For?
RAB Regulus Arcturus Black
RSGFYS Russian Ship Go Fuck Yourself
MBS Miscellaneous Biochemical Shit
USA Universal Stain: Acridine
UA Unnecessary Acronym
RAS Reactive Aggressive Species
TEM Tentatively Excited Mammography
KGB Krushchev-Gorbachev-Brezhnev gene
BSc See “BS”