Protein form and function

Whitehead Institute researchers have identified a protein complex that, when mutated, sends the master growth regulatory pathway known as mTORC1 into overdrive. Researchers believe that mutations in this complex could serve as biomarkers to predict response to rapamycin treatment in cancer patients.

In a surprising finding that helps explain fundamental behaviors of normal and diseased cells, Whitehead Institute scientists have discovered a set of powerful gene regulators dubbed “super-enhancers” that control cell state and identity.

A team of scientists from Whitehead Institute and the University of Texas Southwestern Medical Center has added markedly to the job description of prions as agents of change, identifying a prion capable of triggering a transition in yeast from its conventional single-celled form to a cooperative, multicellular structure. This change, which appears to improve yeast’s chances for survival in the face of hostile environmental conditions, is an epigenetic phenomenon—a heritable alteration brought about without any change to the organism’s underlying genome.

One enzyme, RagA, has been found to regulate the mechanistic target of rapamycin complex 1 (mTORC1) pathway in cells according to glucose and amino acid availability. When this regulation breaks down in fasting newborn mice, the animals suffer a nutritional crisis and die.

According to Whitehead Institute researchers, a protein known as monocarboxylate transporter 1 (MCT1), which is highly expressed in a subset of metabolically altered cancer cells, is needed for the entry of the investigational cancer drug 3-bromopyruvate (3-BrPA) into malignant cells.

By examining the results of genome-wide association studies (GWAS) in conjunction with experiments on mouse and human red blood cells (RBCs), researchers in the lab of Whitehead Institute Founding Member Harvey Lodish have identified the protein cyclin D3 as regulating the number of cell divisions RBC progenitors undergo, which ultimately affects the resulting size and quantity of RBCs.

Whitehead Institute researchers have found that an ancient, highly conserved cell survival factor drives expression of a specific set of genes that is strongly associated with metastasis and death in patients with breast, colon, and lung cancers.

Researchers at Whitehead Institute and Memorial Sloan-Kettering Cancer Center have defined and analyzed the crystal structure of a yeast Argonaute protein bound to RNA.

A clinical trial involving collaboration between researchers at Whitehead Institute and Dana Farber Cancer Institute is now enrolling patients with recurrent or metastatic estrogen receptor-positive (ER+) breast cancer.