Sue Hengren Wickner is an American biochemist and geneticist who is a distinguished investigator and the head of the DNA Molecular Biology section of the National Institutes of Health. [1] Her laboratory is under the National Cancer Institute and is located in the Center for Cancer Research (NCI/CCR). [2]
Sue earned the B.S. degree from American University and the M.S. from Georgetown University. [2] She studied at the Corcoran School of Art and went on to earn her Ph.D. in 1973 from Albert Einstein College of Medicine of Yeshiva University. Her dissertation advisor there was Jerard Hurwitz. [1] She pursued postdoctoral training at National Institutes of Health with Martin Gellert, then joined the Laboratory of Molecular Biology at the National Cancer Institute. [2] She did a sabbatical with Fred Sanger at the MRC in Cambridge UK in 1983.
Sue Wickner and her coauthors Michel Wright, Reed Wickner and Jerry Hurwitz published an early paper showing DNA replication in the test tube. They found that the bacterial virus or phage Phi X174 could be converted from single stranded to the double stranded replicative form in the test tube and that the reaction required the gene products of dnaC, dnaE, and dnaG genes of the phage. [3] At NIH, her research has illuminated the action of proteins that utilize adenosine triphosphate (ATP) energy in tiny machines to replicate DNA, remodel proteins, and break down proteins. She has been a major contributor to the understanding of molecular chaperones, proteins that regulate most cellular processes including replication and transcription and response to stress. Chaperones function to alter activity, refold as well as degrade proteins. [1] Her citation from election to the National Academy of Sciences notes her most recent contributions to ATP-dependent chaperones for proteolysis (protein breakdown), showing how they participate in stress responses by removing proteins that folded incorrectly and how they degrade regulatory proteins once their signals have been delivered. Since there are some human diseases that result from abnormally folded and/or aggregated proteins, these ATP-dependent chaperones are important in disease treatment development. [4]
In molecular biology, molecular chaperones are proteins that assist the conformational folding or unfolding of large proteins or macromolecular protein complexes. There are a number of classes of molecular chaperones, all of which function to assist large proteins in proper protein folding during or after synthesis, and after partial denaturation. Chaperones are also involved in the translocation of proteins for proteolysis.
Heat shock proteins (HSPs) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including exposure to cold, UV light and during wound healing or tissue remodeling. Many members of this group perform chaperone functions by stabilizing new proteins to ensure correct folding or by helping to refold proteins that were damaged by the cell stress. This increase in expression is transcriptionally regulated. The dramatic upregulation of the heat shock proteins is a key part of the heat shock response and is induced primarily by heat shock factor (HSF). HSPs are found in virtually all living organisms, from bacteria to humans.
The 70 kilodalton heat shock proteins are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms. Intracellularly localized Hsp70s are an important part of the cell's machinery for protein folding, performing chaperoning functions, and helping to protect cells from the adverse effects of physiological stresses. Additionally, membrane-bound Hsp70s have been identified as a potential target for cancer therapies and their extracellularly localized counterparts have been identified as having both membrane-bound and membrane-free structures.
Hsp90 is a chaperone protein that assists other proteins to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of proteins required for tumor growth, which is why Hsp90 inhibitors are investigated as anti-cancer drugs.
Stress-induced-phosphoprotein 1 also Hsp70-Hsp90 organising protein (Hop) is encoded in the human by the STIP1 gene. It functions as a co-chaperone which reversibly links together the protein chaperones Hsp70 and Hsp90.
Heat shock 70 kDa protein 8 also known as heat shock cognate 71 kDa protein or Hsc70 or Hsp73 is a heat shock protein that in humans is encoded by the HSPA8 gene on chromosome 11. As a member of the heat shock protein 70 family and a chaperone protein, it facilitates the proper folding of newly translated and misfolded proteins, as well as stabilize or degrade mutant proteins. Its functions contribute to biological processes including signal transduction, apoptosis, autophagy, protein homeostasis, and cell growth and differentiation. It has been associated with an extensive number of cancers, neurodegenerative diseases, cell senescence, and aging.
Endopeptidase Clp (EC 3.4.21.92, endopeptidase Ti, caseinolytic protease, protease Ti, ATP-dependent Clp protease, ClpP, Clp protease). This enzyme catalyses the following chemical reaction
Co-chaperones are proteins that assist chaperones in protein folding and other functions. Co-chaperones are the non-client binding molecules that assist in protein folding mediated by Hsp70 and Hsp90. They are particularly essential in stimulation of the ATPase activity of these chaperone proteins. There are a great number of different co-chaperones however based on their domain structure most of them fall into two groups: J-domain proteins and tetratricopeptide repeats (TPR).
Heat shock 70 kDa protein 1, also termed Hsp72, is a protein that in humans is encoded by the HSPA1A gene. As a member of the heat shock protein 70 family and a chaperone protein, it facilitates the proper folding of newly translated and misfolded proteins, as well as stabilize or degrade mutant proteins. In addition, Hsp72 also facilitates DNA repair. Its functions contribute to biological processes including signal transduction, apoptosis, protein homeostasis, and cell growth and differentiation. It has been associated with an extensive number of cancers, neurodegenerative diseases, cell senescence and aging, and inflammatory diseases such as Diabetes mellitus type 2 and rheumatoid arthritis.
Human gene HSPA1B is an intron-less gene which encodes for the heat shock protein HSP70-2, a member of the Hsp70 family of proteins. The gene is located in the major histocompatibility complex, on the short arm of chromosome 6, in a cluster with two paralogous genes, HSPA1A and HSPA1L. HSPA1A and HSPA1B produce nearly identical proteins because the few differences in their DNA sequences are almost exclusively synonymous substitutions or in the three prime untranslated region, heat shock 70kDa protein 1A, from HSPA1A, and heat shock 70kDa protein 1B, from HSPA1B. A third, more modified paralog to these genes exists in the same region, HSPA1L, which shares a 90% homology with the other two.
Heat shock protein HSP 90-beta also called HSP90beta is a protein that in humans is encoded by the HSP90AB1 gene.
Prostaglandin E synthase 3 (cytosolic) is an enzyme that in humans is encoded by the PTGES3 gene.
Binding immunoglobulin protein (BiPS) also known as 78 kDa glucose-regulated protein (GRP-78) or heat shock 70 kDa protein 5 (HSPA5) is a protein that in humans is encoded by the HSPA5 gene.
DnaJ homolog subfamily B member 1 is a protein that in humans is encoded by the DNAJB1 gene.
Hsc70-interacting protein also known as suppression of tumorigenicity 13 (ST13) is a protein that in humans is encoded by the ST13 gene.
DnaJ homolog subfamily A member 1 is a protein that in humans is encoded by the DNAJA1 gene.
The GHKL domain is an evolutionary conserved protein domain. It is an ATPase domain found in several ATP-binding proteins such as histidine kinase, DNA gyrase B, topoisomerases, heat shock protein HSP90, phytochrome-like ATPases and DNA mismatch repair proteins.
In molecular biology, chaperone DnaJ, also known as Hsp40, is a molecular chaperone protein. It is expressed in a wide variety of organisms from bacteria to humans.
The chaperone code refers to post-translational modifications of molecular chaperones that control protein folding. Whilst the genetic code specifies how DNA makes proteins, and the histone code regulates histone-DNA interactions, the chaperone code controls how proteins are folded to produce a functional proteome.
Mehdi Mollapour is a British-American biochemist and cancer biologist. He is a professor, vice chair for translational research and director of Renal Cancer Biology Program for the Department of Urology, and adjunct professor at the Department of Biochemistry and Molecular Biology at SUNY Upstate Medical University.
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