Flick of a protein switches immune response

July 27, 2006

A single protein can turn on and off a key component of the immune system by changing partners in an elegant genomic dance, said researchers at the University of Southern California and Harvard Medical School.

Because autoimmune diseases – such as arthritis, allergies and dozens of other illnesses – begin when the body's defenses respond at the wrong time or place, the on-off mechanism for the immune system has been the subject of intense study for decades.

The USC-Harvard team studied proteins critical to immune tolerance, a term for the healthy balance between a weak immune system and an overly aggressive, indiscriminate watchdog.

Lin Chen, professor of molecular and computational biology at USC and lead co-author with Harvard's Anjana Rao, said the team's result would "open a big door for people to explain the fundamental mechanism of immune tolerance."

In the July 28 issue of Cell, the USC-Harvard group shows that the protein Nuclear Factor of Activated T cells (NFAT), in collaboration with FOXP3, an essential factor in regulatory T cells, orchestrates a genetic program critical to immune tolerance.

But the same NFAT, paired with a second family of proteins known as AP-1, instead stimulates immune response.

Chen said the finding offers the first strong evidence in favor of the 15-year-old "combinatorial control" theory of gene expression.

According to the theory, the specific expression of a gene depends on the combination of "transcription factors" acting on it. Transcription factors help to translate a gene's instructions into actual proteins. FOXP3 and NFAT are two such factors; the human body contains around 3,000.

"The work provides a structural demonstration of combinatorial control of gene expression," Chen said. "This is, in my view, the most direct demonstration that this is indeed happening in nature."

The researchers were able to identify single genes that were activated by NFAT in combination with AP-1 and suppressed by NFAT with FOXP3.

Beyond shedding light on the immune system, the Cell paper may advance biology and medicine toward a much larger goal: how to turn single genes on or off.

"This [result] has far-reaching implications for understanding the principles of signal transduction and transcriptional networks of living cells," Chen said.

The Cell paper, which Chen describes as spanning 14 years of laboratory work, builds on a result his group published in Nature in 1998.

Source: University of Southern California

Related Stories

Recommended for you

Microsoft describes hard-to-mimic authentication gesture

August 1, 2015

Photos. Messages. Bank account codes. And so much more—sit on a person's mobile device, and the question is, how to secure them without having to depend on lengthy password codes of letters and numbers. Vendors promoting ...

Netherlands bank customers can get vocal on payments

August 1, 2015

Are some people fed up with remembering and using passwords and PINs to make it though the day? Those who have had enough would prefer to do without them. For mobile tasks that involve banking, though, it is obvious that ...

Model shows how surge in wealth inequality may be reversed

July 30, 2015

(Phys.org)—For many Americans, the single biggest problem facing the country is the growing wealth inequality. Based on income tax data, wealth inequality in the US has steadily increased since the mid-1980s, with the top ...

A cataclysmic event of a certain age

July 27, 2015

At the end of the Pleistocene period, approximately 12,800 years ago—give or take a few centuries—a cosmic impact triggered an abrupt cooling episode that earth scientists refer to as the Younger Dryas.

New blow for 'supersymmetry' physics theory

July 27, 2015

In a new blow for the futuristic "supersymmetry" theory of the universe's basic anatomy, experts reported fresh evidence Monday of subatomic activity consistent with the mainstream Standard Model of particle physics.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.