2007-2008 Projects
Brain Eater
Bradford High School
Students:
Maria Barnes, Mahmood Cheema, Tony Clark, Michelle Goettge, David Jensen, Fred Seewald, Steve Snowden, Beth Stebbins, Joshua Swenson
Teacher: Jean Lee
Mentor: Anita Manogaran, Ph.D., University of Illinois – Chicago
Abstract: Many proteins are misfolded and dysfunctional when first formed. Chaperone proteins are used to refold, protect and disaggregate misshapen proteins. While chaperones are traditionally beneficial, it has been recently found they play a role in the formation of infectious protein aggregates. These infectious proteins are called prions and the diseases they cause have no known cure. Prions are responsible for transforming healthy brain proteins into prion replicas, therefore spreading the disease and disrupting normal functions. This transformation occurs when the mainly alpha helical form of the PrPc protein changes into a beta sheet rich protein This conformational change is associated with neurodegenerative disorders in many organisms, such as Mad Cow in cattle, Scrapie in Sheep, and Creutzfeldt-Jacob disease in humans. Prions are found not only in mammals, but in other organisms as well, and have been extensively studied in yeast. One prion in yeast is called [RNQ+] which is the misfolded aggregate form of the Rnq1 protein. The chaperone protein Sis1 binds to the ssa1 chaperone and appears to influence the prion aggregate. Chaperones break the protein aggregate into smaller pieces that can be passed on to many daughter cells. Because the pieces have more sticky ends than the original aggregate, they attract more prions, forming new aggregates. Scientists hope to explore the structure of Sis1 and its peptide binding fragment to further understand how prions work.
Sticky Situations: A Story of the Rebel Mammary Serine Protease Inhibitor
Brown Deer High School
Students:
Charles Bach, Piper Bancroft, Elaine Brushafer, Ellen Cahill, Andrew Faught, Sara Faught, Benjamin Jaberg, Adam Majusiak, Daniel Matz, Kristi Noll, Amy Ramirez, Collin Rice, Karleisa Rogacheski, Justin Schleicher, Cameron Stoeger, Aaron Suggs, Jordan Tubbs
Teacher: Mrs. Gina R. Vogt
Mentors: Sally S. Twining, Ph.D. and Malathi Narayan – Medical College of Wisconsin, Milwaukee, WI
Abstract: In 2007 alone, an estimated 180,000 women and 2,000 men were diagnosed with breast cancer. Malignant cells in breast tissue rapidly reproduce and can metastasize, thus spreading cancerous cells throughout the body. If cells metastasize, they detach from the extracellular matrix (ECM), but if they remain attached to the ECM, cells cannot metastasize. This behavior has been linked to the expression of maspin in mammary cells. Maspin, or Mammary Serine Protease Inhibitor, is a member of the serpin family, members of which deactivate serine proteases, enzymes that cleave proteins which contain serine residues. Serine proteases aid in many functions of the body, including blood clotting and digestion. Maspin adopts a classical serpin protein fold, but is classified as a non-inhibitory/non-classical serpin as it does not have any known serine protease targets to inhibit. Instead, the reactive site loop (RSL) of maspin stimulates the adhesion of cells to the ECM. This action prevents the migration of cells, thus preventing metastasis. It has been found that the RSL of maspin alone is capable of producing the increased adhesion of cells to the ECM. Recent research has determined that substituting alanine for arginine at position 340 in the RSL loop reduces the adhesion of cells to the ECM. Current research is attempting to determine the method by which maspin functions, and which key amino acids on the RSL loop are responsible for increasing cell adhesion. With this new research, scientists are one step closer to developing an effective drug to control the metastasis of breast cancer cells.
HIV-1 Protease: A Paradigm for Structure-Based Drug Design
Edgewood Campus School
Students:
Clare Everts, Emma Green, Walter Grosenheider, Michael Hetsko, Rebecca Jensen, Ana Lynn, Miles Petchler, Julia Pinckney, Jake Power, MacKenzy Price, Kelsey Rayment, Jake Scholz, Connor Spencer, and Alex Wol
Teacher: Dan Toomey
Mentor: Hazel M. Holden, Ph.D., University of Wisconsin, Madison, WI
Abstract: Acquired immunodeficiency syndrome, or AIDS, was first recognized as a diseased state in 1981 and is associated with a depletion of T lymphocytes. It is caused by the human immunodeficiency virus (HIV). Since 1981 more than 25 million people have died of AIDS, and it is believed that over 40.3 million people are presently living with HIV. Proteins on the cell surface of HIV attach to the host cell, enabling the viral membrane and the host membrane to fuse, releasing the viral RNA into the cell. The RNA is then converted to DNA, which is then transcribed and translated. The resulting proteins are long chains that need to be cut into separate proteins by the HIV protease. This cleavage event is essential for the life cycle of the virus because it enables the HIV proteins to become functional. These proteins are then packaged into new viral capsids, which then bud off of the host cell, thus creating several new viruses capable of infecting other cells. The three-dimensional structure of the HIV protease was first solved in 1989, and since then more than 250 structures of it complexed with various inhibitors have been solved. Because of its critical role in viral maturation, scientists have used its structure as a starting point for drug development. Eleven different “protease inhibitors” have been approved by the Food and Drug Administration (FDA). For our project, we have chosen the structure of the HIV-1 protease complexed with Tipranavir (Aptivus®), a nonpeptidic protease inhibitor.
Ubiquitination: The Garbage Cycle of a Cell
Grafton High School
Students:
Dan Burgardt, Lexi Chopp, Ashley Emery, Alyssa Fletcher, Kaleigh Kozak, Adam Schaenzer, Dustin Studelska, Lindsay Wendtlandt, Lindsay Zadra
Teacher: Fran Grant
Mentor: Namitha Vishveshwara, University of Illinois at Chicago
Abstract: Within every cell, there exists a system known as the ubiquitin-proteasome system (UPS) that eliminates damaged, misfolded or excess proteins. Unwanted proteins are tagged with ubiquitin, a small protein that identifies other proteins as being ready for degradation. The process of activating and transferring the ubiquitin to the protein is referred to as ubiquitination. Three proteins involved in this process are the ubiquitin activating enzyme (E1), the ubiquitin conjugating enzyme (E2), and the ubiquitin ligase (E3). Ubiquitination begins with ubiquitin being activated by and attaching to E1. E1 transfers ubiquitin to E2. Then E2 delivers ubiquitin to the unwanted protein, either directly or through E3. Finally, the tagged protein is broken down by the proteasome, which is the cell’s protein-degrading complex. E2 plays a critical role in the ubiquitination process. Ubch5b is one of many E2s that is involved in tagging unwanted proteins with ubiquitin. Researchers are studying the relationship between the yeast Ubch5b and a specific form of misfolded protein called prions. Prions are unique because when one protein takes the prion form, correctly folded proteins also misfold into prions and aggregate. Prions are infectious proteins; they are not viral or bacterial. Mad cow disease is caused by the presence of prions. In yeast, when Ubch5b is deleted, it leads to increased prion formation. The exact role of the yeast Ubch5b in increased yeast prion formation is still unknown.
Botulinum Neurotoxin Serotype A (BoNT/A)
Kettle Moraine High School
Students:
Greg Dams, Jeff Dougherty, Disa Drachenberg, Michael Goelz, Alex Hoffman, David Kasper, Kris Krause, Tom Lankiewicz, Jacob Laux, Melanie Mayes, Nathan Murray, Kaitlin Swanson, Marsha Tessman, Brandon Williams
Teachers: Peter Nielsen, Karen DeBoer, Steve Plum
Mentor: Joe Barbieri, Ph.D. Medical College of Wisconsin, Milwaukee, WI
Abstract: Clostridium botulinum, which causes botulism, is a bacterium found in soil and in improperly processed foods. Botulism causes neuroparalytic diseases, where paralysis results in a part of the body because the nerves that supply it are diseased. Common symptoms of botulism usually appear twelve to 36 hours after consumption and include a dry mouth, difficulty swallowing, slurred speech or difficulty speaking, muscle weakness, blurred or double vision, and drooping eyelids. Botulism works by blocking the release of neurotransmitters – chemicals that transmit information to, from, and within the brain – through the action of clostridal neurotoxins (CNTs) that break down soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, which are essential for fusion of the vesicle carrying the neurotransmitters with the cell membrane, thus releasing the neurotransmitters. If the neurotransmitters are not released, communication between nerve and muscle cells is halted, thus leading to paralysis. Botulinum toxins (BoNTs) are composed of three domains: receptor, translocation, and catalytic. The receptor domain of BoNTs binds to receptors in the surface of neurons and enters the neuron by receptor-mediated endocytosis. Once inside the neuron, the catalytic domain is translocated across the membrane of the vesicle by the translocation domain, into the cytosol, where the catalytic domain cleaves SNARE proteins. This blocks the release of neurotransmitters and leads to paralysis.
The Human ß2-Adrenergic Receptor Bound to a Beta Blocker and the Role of G Protein-Coupled Receptors
Madison West High School
Students:
Dianna Amasino, Axel Glaubitz, Susan Huang, Joy Li, Hsien-Yu Shih, Junyao Song, Esther Yoon, Xiao Zhu
Advisor: Basudeb Bhattacharyya
Assistant: Peter Vander Velden
Mentor: David Nelson, Ph.D. and Jim Keck, Ph.D., University of Wisconsin-Madison, Madison, WI
Abstract: G protein-coupled receptors (GPCRs) are the largest family of integral membrane proteins coded by the human genome. GPCRs are important for signal transduction with the general structural characteristic of a plasma membrane receptor with seven transmembrane segments. More than 50% of human therapeutics act on GPCRs, but these drugs only interact with a fraction of the GPCRs. One example of a GPCR targeted by pharmaceutical companies is the ß2-adrenergic receptor. Adrenergic receptors are found throughout the body and are triggered by the hormone epinephrine (also known as adrenaline, hence the name adrenergic). When epinephrine binds to the receptors, it causes a slight conformational change within the receptor. This change then triggers activation of a G-protein (proteins that bind GTP and are coupled to the receptor on the cytoplasmic side of the receptor) causing dissociation of the G-protein from the receptor). Through the transfer of GTP, G-protein activates an enzyme that converts ATP into cyclic AMP, which induces a response within the cell (for example, muscle contraction if the receptor is located on a muscle cell). When this signal transduction event functions normally in the body, it helps regulate heart rate and blood pressure and is important for the “fight or flight” response. It is important medically to be able to manipulate these functions in cases of high blood pressure or heart failure through the use of beta blockers, a medicine designed to bind to adrenergic receptors, thus inhibiting the binding of epinephrine, and resulting in a lack of effect of the hormone on the body. We have used rapid prototyping technology to model the interaction of the human ß2-adrenergic receptor with the beta blocker, carazolol. The structure is dominated by seven alpha helices and is representative of the structure of GPCRs. By modeling the ß2-adrenergic receptor, we hope to better understand GPCRs as well as understand the mechanism of hormone/drug binding, which will aid in developing better drug treatments.
H-Ras GTPase: Key to Understanding Cancer?
Marquette University High School
Students:
Mohammed Ayesh, Wesley Borden, Andrew Bray, Brian Digiacinto, Patrick Jordan, David Moldenhauer, Thomas Niswonger, Joseph Radke, Amit Singh, Alex Vincent, and Caleb Vogt
Teachers: Keith Klestinski and David Vogt
Mentor: Evgenii Kovrigin, Ph.D., Medical College of Wisconsin, Milwaukee, WI
Abstract: The protein known as H-Ras GTPase is essential to proper biological functioning in the entire web of life. The main function of this protein is giving the "stop" signal to the process of cell reproduction. Unfortunately, this protein is not perfect and severe consequences, such as cancer, can arise when H-Ras GTPase malfunctions.
H-Ras GTPase is a protein from the large family of enzymes that bind and split GTP. H-Ras GTPase is vital in processes like cell-to-cell communication, protein translation in ribosomes, and programmed cell death (apoptosis). Its main fields of operation are determining stem cell into specific functioning cells, as well as replicating preexisting "specialized" cells. All G domain based proteins have a universal structure and two universal switch mechanisms, which consist of a mixed, six-stranded betasheet and five alpha helices. H-Ras GTPase works by first dissociating from GDP and binding to GTP, activating the protein. Then it binds to another G-protein to enact a cell response. After interaction, the GTP is hydrolyzed to GDP, turning off the switch.
H-Ras GTPase has a high affinity for both GDP and GTP. This affinity for GDP impairs the switch from turning off, which can lead to serious problems, such as cancer. When GTPase bonds to GTP, the molecular switches change shape. This newly shaped GTPase now bonds to a protein to transmit instructions. Since H-Ras GTPase is central to cell division, slight mutations in the protein cause the switch to be "stuck-on," resulting in hyperactive cell growth and division. These oncogenic mutations in H-Ras GTPase are responsible for nearly 30% of all human-form cancers.
Heparin-Induced Thrombocytopenia & Thrombosis
Messmer Catholic High School
Students:
Carolina Herrara and Maya Bates-Muhammad
Teachers: Carol Johnson
Mentors: Debra Newman, Ph.D., Blood Center of Wisconsin, Milwaukee, WI
Abstract: HIT, or Heparin-Induced Thrombocytopenia, is a life-threatening complication that can occur during major surgery when the anti-coagulant Heparin is administered. This complication occurs when Heparin binds to Platelet Factor 4, which is a protein that is released from activated platelets. Platelets circulate in the bloodstream, and are important for coagulating blood. When a blood vessel is damaged, platelets bind to and cover the damaged site, sticking together to form a "thrombus," and initiate vessel repair. Heparin is a negatively charged polysaccharide that binds tightly to the positively charged tetramer, PF4. This binding produces a conformational change in the PF4 protein that causes the body's immune system to produce antibodies against the newly shaped PF4. When the PF4-heparin complex then binds to platelets, the antibodies produced against the PF4 bind to the PF4-Heparin-Antibody complex and can cause two things to occur. First, the antibody-coated platelets are removed from the circulation, resulting in thrombocytopenia. Second, the antibodies can activate the platelets to which they are bound, resulting in thrombosis. Thrombocytopenia is a condition in which platelets are too few or inactive resulting in excessive bleeding. Thrombosis is a condition in which platelets are too numerous or active and can block blood flow and result in heart attack, stroke, or loss of limbs. Researchers at BloodCenter of Wisconsin and elsewhere study how antibodies bind to PF4-heparin complexes so that they can find ways to interfere with antibody binding and prevent the thrombocytopenia and thrombosis that complicate treatment of patients who take heparin.
21st Century Drug Design: Blocking Prokaryotic Cell Wall Synthesis by Stopping DHPR
Nathan Hale High School
Students:
Pravleen Bajwa, Kenton Chodara, Nicole DeGoerge, J.J. Garsombke, Tim Jesse, Rebecca Ruechel, Kristin Zorr
Teachers: Sue Getzel and Anne Xiong
Mentor: Dan Sem, Ph.D., Marquette University, Milwaukee, WI
Abstract: The bacteria Mycobacterium tuberculosis is the causative agent for tuberculosis (TB) and has been present since at least 2400 BCE. Two million people worldwide die from it annually, with the highest death rates in developing countries. This resurgence of TB can be attributed to many factors, one of which is the bacteria’s increasing resistance to a broad spectrum of antibiotics. In TB, antibiotics act to cause leakage in the prokaryotic cell wall, which leads to cell death. Resistant bacteria have acquired mutations in key enzymes involved in cell wall formation, thus preventing antibiotics from inducing wall leakage. Therefore a need exists for development of new types of drugs to inhibit or kill infectious bacteria. One new path includes targeting an enzyme, Dihydrodipicolinate reductase (DHPR), which is used to produce prokaryotic cell walls. When this enzyme is inhibited, the cell wall of M. tuberculosis becomes unstable, killing the bacterium. DHPR catalyzes a chemical reaction in the metabolic pathway leading to diaminopimelate, an essential cell wall component. If DHPR can be inhibited by a substrate competitor, then a potential drug lead may be identified. Understanding how the enzyme’s active sites function will facilitate the optimization of a recently designed inhibitor of DHPR. Specifically, the research will explain how this molecule may interact with the 4 binding pockets on DHPR. For this drug to work, is binding required at 1, 2, 3 or all 4 pockets, and why? Does binding at one pocket affect what goes on at the other 3? These questions need to be answered before a drug molecule can be rationally engineered against DHPR.
Construction of a physical model of a farnesyltransferase-inhibitor complex. Insight into a novel therapy for Hutchinson-Guilford Progeria
Riverside University High School
Students:
Maikeng Her, Ardyce Jackson, Tracy Bradley, Hydiza Hassan, Ammy Lee, Tommy Lee,
Qualandra Brookens, Jennifer Donahoe, Jessica Jimenez, Kenneth Caldwell,
Damaris Hurtado, Elizabeth Montes, Ia Moua, Athee Xiong
Teacher: Jeff Anderson
Mentor: Bob Deschenes, Ph.D., Medical College of Wisconsin, Milwaukee, Wisconsin
Abstract: The Riverside SMART Team (Students Modeling A Research Topic) created a 3D physical model of a farnesyltransferase (FTase)-inhibitor complex and discussed its significance in the development of a novel therapy for Hutchinson-Guilford Progeria. Farnesyltransferase inhibitors (FTIs) were originally designed as anti-cancer drugs, but recently have been shown to slow premature aging resulting from Progeria (1). This premature aging syndrome is caused by a mutation that affects processing of the lamin A protein, a component of the nuclear lamina. A farnesylated prelamin intermediate accumulates, which in turn interferes with the assembly of a functional nuclear lamina. Farnesylation of prelamin A occurs on a CaaX box motif by the FTase. One class of FTIs structurally mimics the CaaX motif thereby inhibiting the enzyme. Inhibition of lamin A farnesylation prevents the accumulation of farnesyl-prelamin A and inhibition of lamina assembly. This surprising discover has given clinicians the first drug to treat this rare, but deadly premature aging syndrome. By studying the structure of FTIs bound to farnesyltransferase, more new specific drugs might be found.
(1) Meta, M, Shao, H., Yang, Bergo, M.O., Fong, L., Young, S.G. (2006) Protein farnesyltransferase inhibitors and progeria. Trends in Molecular Medicine
12:480-487
RNA Polymerase II: The Reader of the Secret Code!
St. Dominic Middle School
Students:
Grace Buting, Teddy Delforge, Meg Donovan, Erika Engel, Teddy Esser, Ellen Fink, Maura King, Meredith Klinker, Billy MacDonald, Katie Mark, Stephanie McGavin, Vince Moldenhauer, Paige Pichler, Nathan Rein, Katie Rieger, Hailey Rowen, Stephanie Seubert, Rachel Sladky, Ariana van Willigen
Teacher: Donna LaFlamme
Mentor: Vaughn Jackson, Ph.D., Medical College of Wisconsin
Abstract: RNA polymerase II is essential to life in cells. Found in the nucleus of a cell, this molecule is a multi-subunit protein. RNA Pol II makes messenger RNA (mRNA) copies of genes. This process is called transcription and is the first step in protein synthesis. Genes are made of DNA and contain the codes for making proteins. Since DNA is unable to leave the nucleus, RNA Pol II makes an mRNA copy that can leave the nucleus. Ribosomes then attach to and read the mRNA. They synthesize a protein by joining amino acids in the correct order. RNA Pol II has 12 subunits and the two largest, Chain A and Chain B, contain the active site where the enzyme adds fifty to ninety nucleotides per second to the growing mRNA strand. Pol II is very accurate, only making about 1 mistake every 10,000 nucleotides. When it does make a mistake or finds DNA damage, it can backtrack to correct the error. Roger Kornberg and his research group hypothesize that during transcription the bridge helix changes shape to ratchet the DNA template and transcript through the active site while holding the end of the transcript in place. When the poison alpha-amanitin found in the Death Cap Mushroom paralyzes the bridge helix, transcription slows from 50 to 90 nucleotides per second to 2 to 3 nucleotides per minute. At this slow transcription rate, mRNA copies of genes do not get made, protein synthesis stops, and cells die. Untreated alpha-amanitin poisoning usually causes death within 10 days.
Dr. Helix and Mr. Sheet: The two faces of a-synuclein
Wauwatosa East High School
Students:
David Covell, Nate Deisinger, Neha Hasan, Brian Hoettels, Kelly Hubert, Elyssa Kenagy, Nate Kolpin, Matt Marti, Lucia Roegner
Teacher: Mary Anne Haasch
Mentor: Jason Kowalski, Medical College of Wisconsin, Milwaukee, WI
Abstract: a-synuclein is a protein that affects thousands of people, yet very little is known about it. This protein is associated with neurodegenerative diseases including Parkinson’s Disease (PD) and Lewy Body Dementia (LBD). PD affects 500,000 people every year, and is linked to degeneration of motion control centers in the brain. LBD is a disorder that affects cognitive, autonomic, and sleep ability in people over 65. a-synuclein is involved in synaptic vesicle pools, dopamine regulation, formation of soluble N-ethylmaleimide-sensitive factor (SNARE) complexes which help vesicles fuse with the membrane, and other less studied regulatory functions. a-synuclein’s most understood function is the regulation of vesicle pools in neurons. When no a-synuclein is present, vesicles dock with a membrane and are ready to fuse with it and release neurotransmitters, sending signals to the brain. When a-synuclein accumulates, the vesicles are prevented from fusing and releasing neurotransmitters. In varying environments, a-synuclein can take the shape of an a-helix, ß-sheet, or be unstructured. For instance, a-synuclein is unstructured until it is brought near a membrane, when it takes an a-helical conformation, an advantage to fusing with a membrane. The ß-sheet conformation is found primarily in Lewy Bodies in PD and LDB patients. In order to understand a-synuclein’s role in PD and LBD, scientists must learn more about its structure and function.
DRB3*0101: Mother Doesn’t Always Know Best
Wauwatosa West High School
Students:
Matt Berggruen, Connor Grant, Chris Hampel, Jessica Hoffmann,
Sean Kundinger, Rituparna Medda, Katie Omernick, Mariah Rogers, Chandresh Singh
Teacher: Donnie Case
Mentor: Andrea Ferrante, MD, Blood Research Institute
Abstract: Fifteen to forty percent of intensive care infants have Neonatal Alloimmune Thrombocytopenia (NAIT). This disorder may result in intracranial hemorrhaging, potentially causing death. NAIT is commonly associated with depletion of fetal platelets due to maternal antibodies against a specific glycoprotein located on the platelet cell surface. Glycoprotein IIb/IIIa has a region known as HPA1, which has a specific dimorphism linked to NAIT. If the mother’s platelet has a proline residue in position 33 (HPA1b), and the baby has leucine at this same position (HPA1a), the mother will mount an immune response against the baby’s platelets, as she sees them as foreign. Maternal B cells produce antibodies anti-HPA1a. The antibodies bind to the platelets and these antibody-coated platelets are then marked for destruction, leading to clotting disorder. Interestingly, mother responders are characterized by the expression of class II HLA DRB3*0101 (also known as DRw52a with other nomenclature) on the surface of Antigen Presenting Cells. Class II HLA molecules play an important role in the initiation of the immune response presenting antigenic peptides and stimulating helper T cells. This high HLA association may suggest that the B cells require T cell help. Thus, under the hypothesis that the same dimorphism may generate both the B cell target and constitute the HLA-bound peptide, T cells specific for the HPA1 antigen have been identified, supporting the existence of a HLA II/HPA1a complex. Here we present the crystal structure of HLA DRB3*0101 in complex with HPA1a antigen, whose exploration may provide insights as to the understanding of this and other allele-associated diseases.
Initiating Cell Division: The Role of the Ternary Complex
Whitefish Bay High School
Students:
Zixiao Chen, Youngjoon Choi, Justin Fenzl, Anna Gibson, Alison Huckenpahler, Zak Kaplan, Tim Murray, Sam Roth, Martin Steren
Teachers: Marisa Roberts and Judy Weiss
Mentor: Ravi Misra, Ph.D. and Mary Holtz, Ph.D., Medical College of Wisconsin, Milwaukee, WI
Abstract: DNA, the fundamental building block of cells, tells the cell how to produce proteins, regulate cell division, and pass genetic information from parent cell to daughter cell. However, a human’s DNA is over three billion bases long, and transcribing the entirety of the DNA to get a duplicate of a small section is highly inefficient. To combat this, DNA contains specific sequences that work in conjunction with proteins to signal where to begin and end copying for a specific section. One such sequence of nucleotides is the Serum Response Element (SRE). The SRE is bound by a protein called Serum Response Factor (SRF). SRF binds as a dimer to the minor groove of DNA (red and green structures on gray DNA helix, above). SRF, in combination with SAP-1, another protein, bind to DNA at the SRE. The SAP-1 protein contains two parts: the SAP-1 b-Box that binds to SRF, and the SAP-1 ETS domain that binds to DNA. These two parts are linked with a flexible chain of amino acids, shown above as the gold dotted line. Together, SRF and SAP-1 form a ternary complex with DNA that marks the DNA for transcription. SRF regulation of gene transcription plays an important role in embryonic development, possibly aiding in heart development. Mouse embryos devoid of SRF die early in development, never coming to term. When transcription of the mRNA is misregulated, SRF can cause cancer. This specific ternary complex binds to a portion of the genome that starts the transcription of the human c-fos proto-oncogene when the cell is externally stimulated. Research on this complex is still continuing and scientists are getting closer to understanding its full potential.
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