DRAK2 was a molecule that I conducted research on back in a UCI laboratory for the Department of Immunology. And at the time I picked it because it sounded cool and somehow reminded me of Dracula, but I didn't think too much of it because it seemed like a silly idea. But after some reflecting on this real-life death-inducing molecule, I've come to realize that the founder of DRAK2 and probably everyone in my lab was already in on the pun. So here's my ancient recount on the tale of DRAK2. Oh, and read to the end for a bonus addition of my personal encounter with Count Dracula (cue maniacal laugh*). -VF
DRAK2 TRANSLOCATES IN T-CELLS (& B-CELLS)
T-cells possess the means to kill infected cells, and if not properly regulated, they can cause uncontrollable damage to normal, healthy cells, resulting in autoimmune disorders (source). DRAK2 is such an immunoregulatory molecule that negatively regulates T-cells and B-cells (like a chaperone), and is especially operative in developing and mature lymphocytes (source).
FREAKY FACT: Although Bram Stoker's Gothic novel Dracula popularised the idea of vampires being mythical creatures from Transylvania, the greatest number of real tombs with impaled corpses (about 100 found) assumed have been considered vampires were found in Bulgaria (source). Death-Associated Protein Kinase 4 Family
Though DRAK2 is a serine/threonine kinase that’s a member of the (DAPk)4 family that possess abilities to potentiate apoptosis, DRAK2 serves as a mediator to a multitude of cell-death signaling pathways. As a negative regulator, DRAK2 sets the sensitivity of naïve T-cell activation. Defects can lead to disorders that include cancer, neurodegenerative diseases, and autoimmune diseases (source).
FREAKY FACT: Bram Stoker’s 1897 novel also portrays the fears and anxieties of Victorian society during the Industrial Revolution when the advent of new technologies caused shifts in women's choices to work, in sexual freedom, increased oversight in science research, etc. (source).UV Radiation Exposure Triggers DRAK2
In light of death signals, one of the extracellular stimuli that induce DRAK2 to initiate apoptosis so happens to be UV irradiation (the others being protein molecules like Interleukin-2) (source). As an infamous culprit to skin cancer, UV light can also directly cause cell death by breaking double-stranded DNA and activating other signaling molecules that regulate cell survival (source).
FREAKY FACT: There's a very rare disease called porphyria (also called the "vampire" or "Dracula" disease) that causes vampire-like symptoms, such as extreme skin blistering upon exposure to sunlight, reduced number of red blood cell count, and sometimes hairiness (source). Autophosphorylation of DRAK2
To activate the kinase, DRAK2 goes through a transformational modification of its protein structure that involves a process of auto- (selfie) and trans- (groupie) phosphorylation (source). Upon stimulation, the kinase catalyzes this phosphorylation reaction on its active site with the inception of a phosphate most commonly from ATP, the cell’s energy currency (source).
FREAKY FACT: Though capes were a real trend during the 1800s, they are innately magical - its etymology has the same root as “escape,” as in “to get away.” In other words, it bestows one power to evade problematic circumstances, making Dracula or any wearer quite the formidable foe (source).DRAK2 TRANSLOCATES INTO THE NUCLEUS
Once activated, DRAK2 translocates and accumulates in the nucleus with the help of a built-in honing mechanism known as the nuclear-localization signal (NLS) sequence, and awaits further notice (source). A factor in the nucleus, which is likely the ultimate target of DRAK2 phosphorylation, may corroborate with other effectors to transduce the apoptotic signal of DRAK2 (source).
FREAKY FACT: During medieval Europe, villagers blamed vampires for unexplainable misfortunes like a bad harvest. When they unearthed graves to check, the bodies would pop up with seemingly fresh blood from their mouths, which was unknowingly caused by a delayed intestinal putrefaction process (source). DRAK2 Recruits the Final Executors
Based on its structure, DRAK2 is unlikely to possess the protease-type abilities that actively breakdowns cells, but may instead work as an agent that transfers apoptotic signals into the nucleus. However, several other proteins are translocated into the nucleus along with DRAK2, many of which have the DNase or protease actions that can work as effectors in the execution of apoptosis (source).
FREAKY FACT: The real-life muse behind Dracula, Vlad III or Prince of Wallachia, consolidated his power by inviting hundreds of feuding boyars to a banquet, and would stab his unknowing guests before impaling their still-twitching bodies. Through various methods, he has killed ~80,000 people (source).DRAK2-/- Cells ARE more sensitive to STIMULI
While its abnormal expression induces death, oddly enough there’s no difference in mice missing the molecule entirely (DRAK2−/−) unless exposed to a toxin like SEB; then, mass T-cell death ensues (source). The paradox of DRAK2−/− being resistant to autoimmune disorder yet possesses hyperactive T-cells suggests that DRAK2 promotes the survival of T-cells during clonal expansion (source).
FREAKY FACT: In 2012 the Municipal Council of Zarozje issued a public health warning to residents, instructing them to place garlic and holy crosses around their homes. The reason: Sava Savanovic, Serbia’s most notorious vampire, was apparently on the loose (source). DRAK2 negatively regulates Ca2+
The primary way DRAK2 maintains control of T-cell activation is by negatively regulating calcium mobilisation, which is also critical for the balance between life and death for many cell types. Without DRAK2 signaling, T-cells require greater tonic signaling for structure maintenance during clonal expansion. Like a police on duty, DRAK2 is judiciously crucial for T-cell survival (source).
FREAKY FACT: There is a real vampire community in New Orleans that started in the mid-70s that practices sanguinarian (blood) and psychic feeding – taking energy by physical touch (hands, sexual), astral feeding (mind), or through emotions (source). DRAK2 -/- promotes positive selection
Despite augmented T-cell activation in the presence of an antagonist, DRAK2−/− mice (all cells are missing the receptor entirely) are resistant to EAE, an autoimmune demyelinating disease that resembles multiple sclerosis (source). The role of DRAK2 in the positive selection for T-cell survival highlights the potential of DRAK2 blockade for the permanent prevention of autoimmune T-cell destruction by intrinsic apoptosis pathway (source).
FREAKY FACT: Physical immortality is not currently available, but transhumanism (H+) – a movement of evolving beyond human limits with biotechnology, nanotechnology, bionics, merging with machines, etc. – increases the potential with every advancement (source).BONUS EDITION
FREAKY FACT: I performed the role of Renfield in my high school’s production of Bram Stoker’s 1897 novel Dracula. The character was originally a deranged, male asylum patient, but I took artistic license with my role and evolved Renfield into his female counterpart. My Renfield still maintained the propensity for consuming vermin - just with an additional hemorrhage of class fashioned in a burgundy Victorian dress (which I hand-dyed to match the sanguine tone of the story). As someone who tends to be chronically reserved, I was drawn to this socially-accepted outlet for openly exorcising personal demons that were lurking just beneath my psyche ... and possibly in the shadow of the masses ... (cues ominous music*).The Tale of Renfield meets the Tale of Drak2
The screenplay Dracula is an examination of insanity from multiple perspectives — the various manifestations, how its perception can be skewed by societal norms, and the power dynamics involved. The original Renfield was forced into an insane asylum after succumbing to his neuroses, and those around found him too abnormal to be around proper society. The administrator of the asylum, Dr. Seward, would create a new category of mental illness for Renfield: "My homicidal maniac is of a peculiar kind. I shall have to invent a new classification for him, and call him a zoophagous (life-eating) maniac” (Stoker 80). Unknowing to those around him, Renfield was actually being manipulated remotely by the predator Count Dracula through mind control, though he was preferred as a slave rather than sustenance as he didn’t pass ”sanity standards.” In tandem, Renfield had an obsession over control — he would consume smaller species and progressively move up the food chain as a way to feel like a “higher being” of power. He believed blood imbued one with powers because his controller fed on it for strength, and thus would express his motives with the Scriptural phrase: “For the blood is the life.”
“My homicidal maniac is of a peculiar kind. I shall have to invent a new classification for him, and call him a zoophagous (life-eating) maniac.”
DRACULA VS DRAK2
To not give any other spoilers away, I’ll just say that character Renfield may not have been a lead hero to aspire to be per se, and maybe more of a metaphor of the deranged slave that resides in the psyche of the regular Joe(sephine?). However, s(he) also represents the potential that any madman (accused by society or self-proclaimed alike) has for developing rationality when forced to confront one’s humanity in the eyes of another victim. As for the “Tale of Count DRAK2,” parallels in our inner cellular world can be found with our outer turmoil, with the presence of similar factors that make us vulnerable to external circumstances (e.g. UV radiation) to the power dynamics involved in survival (e.g. regulators and effectors). Ultimately, like DRAK2, negative influences may just be necessary for the positive selection of more noble characteristics that push the evolution of mankind. -VF
Dracula (1931): Martin (Charles K. Gerrard) tries to reason with Renfield (Dwight Frye) but his obsession with eating spiders is all-consuming.