Tag: Protein Function

Model for the architecture of the CCAN

Architecture of protein complex hints at its foundational function in chromosome segregation

November 19, 2015

The Constitutive Centromere-Associated Network (CCAN) plays a foundational role in the machine that directs chromosome segregation during cell division. On the left is a model of the complete machine (the kinetochore) attached to the microtubule that provides the power for chromosome segregation. The right side depicts the direct interactions between CCAN sub-complexes based on Whitehead scientists’ research as viewed from above the CENP-A nucleosome, either occuring on a single nucleosome (top) or or between two nucleosomes (bottom).”

Schematic showing how amino acid inputs control the activity of the growth-regulating mTORC1 pathway

Scientists discover essential amino acid sensor in key growth-regulating metabolic pathway

October 8, 2015

Whitehead Institute scientists have at last answered the long-standing question of how the growth-regulating pathway known as mechanistic target of rapamycin complex 1 (mTORC1) detects the presence of the amino acid leucine—itself a key player in modulating muscle growth, appetite, and insulin secretion.

Diagram of antiparallel beta-sheet structure of the enzyme catalase

Enhanced-sensitivity NMR could reveal clues on how proteins fold

October 8, 2015

Until now, it has been difficult to fully characterize the different structures that proteins can take on in their natural environments. However, using a new technique known as sensitivity-enhanced nuclear magnetic resonance (NMR), Whitehead Institute and MIT researchers have shown that they can analyze the structure that a yeast protein forms as it interacts with other proteins in a cell.

Microscope image of a B lymphocyte showing the location of the mitochondria in relation to the nucleus and plasma membrane

Hydrogen peroxide induces signals that link the mitochondrial respiratory chain to specific cellular pathway

October 5, 2015

Countering the prevailing theory that cellular hydrogen peroxide signaling is broad and non-specific, Whitehead Institute scientists have discovered that this reactive oxygen species (ROS) in fact triggers a distinct signal transduction cascade under control of the mitochondrial respiratory chain—the Syk pathway—that regulates transcription, translation, metabolism, and the cell cycle in diverse cell types. Hydrogen peroxide and other ROS mediate cellular responses in aging and myriad common chronic diseases, including diabetes, heart disease, stroke, cancer, and neurodegeneration. Understanding how these signals function may point to new therapy targets for these conditions.

Diagram of RAB35's role in oncogenesis

New role for an old protein: Cancer causer

September 3, 2015

A protein known to play a role in transporting the molecular contents of normal cells into and out of various intracellular compartments can also turn such cells cancerous by stimulating a key growth-control pathway.

Slides of tagged cells

Cellular recycling complexes may hold key to chemotherapy resistance

September 2, 2015

Upsetting the balance between protein synthesis, misfolding, and degradation drives cancer and neurodegeneration. Recent cancer treatments take advantage of this knowledge with a class of drugs that block protein degradation, known as proteasome inhibitors. Widespread resistance to these drugs limits their success, but Whitehead researchers have discovered a potential Achilles heel in resistance. With such understandings researchers may be able to target malignancy broadly, and more effectively.

Diagram of CDPK1 in its active and inactive forms

Tiny antibodies point to vulnerability in disease-causing parasites

August 24, 2015

By teasing apart the structure of an enzyme vital to the parasites that cause toxoplasmosis and malaria, Whitehead Institute scientists have identified a potentially ‘drugable’ target that could prevent parasites from entering and exiting host cells.

Electron microscope image of a mitochondrion

Amino acid shortage curbs proliferation in cells with mitochondrial dysfunction

July 31, 2015

According to Whitehead Institute researchers, cells with malfunctioning mitochondria are unable to proliferate due to a shortage of the amino acid aspartate, not because of an energy crisis, as was once thought. Mitochondrial dysfunction plays a role in a host of relatively rare disorders as well as neurodegenerative disorders, including Parkinson’s disease.

Transmembrane protein SLC38A9 appears to act as a nutrients sensor for the mTORC1 metabolic pathway

Scientists identify first nutrient sensor in key growth-regulating metabolic pathway

January 7, 2015

Scientists in the lab of Whitehead Institute Member David Sabatini have for the first time identified a protein that appears to be a nutrient sensor for the key growth-regulating mTORC1 metabolic pathway. 

Diagrams of DNA "goody bags"

Special chromosomal structures control key genes

October 7, 2014

Scientists have long theorized that the way in which the roughly three meters of DNA in a human cell is packaged to fit within a nuclear space just six microns wide, affects gene expression. Now, Whitehead Institute researchers present the first evidence that DNA structure does indeed have such effects—in this case finding a link between chromosome structure and the expression and repression of key genes.

Diagram of the Sestrins' role in mTORC1 regulation

New protein players found in key disease-related metabolic pathway

September 25, 2014

Cells rely on the mechanistic target of rapamycin complex 1 (mTORC1) pathway—which senses the availability of nutrients—to coordinate their growth with existing environmental conditions. The lab of Whitehead Member David Sabatini has identified a family of proteins that negatively regulate the branch upstream of mTORC1 that senses amino acids, the building blocks of proteins.

Images of tissue sections from breast cancer patient biopsies

Master heat-shock factor supports reprogramming of normal cells to enable tumor growth and metastasis

July 31, 2014

Long associated with enabling the proliferation of cancer cells, the ancient cellular survival response regulated by Heat-Shock Factor 1 (HSF1) can also turn neighboring cells in their environment into co-conspirators that support malignant progression and metastasis.


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