Researchers reveal a surprising new role for a key protein in cell division

Scientists at the Ruđer Bošković Institute (RBI) in Zagreb, Croatia, have discovered that the CENP-E protein, long thought to be a motor driving chromosomes into place during cell division, actually plays a completely different role in chromosome movement. It stabilizes the first attachments of chromosomes to the internal “tracks” of the cell, ensuring that they align correctly before being divided.

In a related study, scientists discovered that small structures inside our cells called centromeres, once thought to function independently, help guide this key protein that ensures cells divide properly. The findings overturn two decades of theoretical understanding and have major implications for the life sciences, since errors made in this process are the cause of many cancers and genetic diseases.

Every second, billions of times, your body does something that is nothing short of miraculous. A single cell prepares to divide, carrying three billion letters of DNA, and somehow ensures that both daughter cells receive perfect copies.

If this balance shifts, the consequences are immediate and disastrous. A single misplaced chromosome can derail development, fuel infertility or trigger cancer. Cell division is one of the most ruthless games in biology.

For years, scientists thought they had identified at least one of its main players: CENP-E, described as a powerful motor that transports parasite chromosomes to the center of the cell for orderly division. The story was neat, elegant and fake.

Two new RBI studies, published in Natural communications and led by Dr. Kruno Vukušić and Professor Iva Tolić dismantled this model and proposed new ways to regulate it.

Dr. Vukušić completed his postdoctoral training in an ERC Synergy team and is preparing to establish his own research group at the RBI. Professor Tolić, cell biologist and head of the Cellular Biophysics Laboratory at RBI, is a member of EMBO and Academia Europaea.

Together, their expertise and vision drove this research, revealing that CENP-E is not the “muscle” of the operation, but the missing key regulator, the factor that flips the switch at the right time, allowing the cellular choreography to unfold.

“CENP-E is not the engine that attracts chromosomes to the center,” explains Vukušić. “That’s the factor that ensures they can attach properly in the first place. Without that initial stabilization, the system stalls.”

A city with endless traffic

Imagine rush hour in the biggest city. You can imagine millions of cars, millions of intersections. A single error can crash the entire system.

Now reduce this image to the micrometer scale of a cell. Chromosomes are trains, each carrying a cargo of DNA. Microtubules, the fine fibers of the cell skeleton, make up the rails. For the division to be successful, each train must enter the tracks coming from the correct direction and line up at the central station.

The old model made CENP-E the locomotive, putting the laggards in place. The Zagreb team found something more subtle: CENP-E is not the train but the missing coupling element, the mechanism ensuring that the coupling is strong enough to hold. Without this, trains stall near the station, unable to move forward.

When the lights refuse to change

Why do chromosomes hesitate at the edges? The answer lies in Aurora kinases, a family of proteins that act like overzealous traffic lights. They flood the cell with “red” signals, destabilizing early attachments and preventing chromosomes from locking in the wrong place too early.

This protection avoids errors near the cell poles but also risks producing too much red and not enough green. Here, CENP-E intervenes. By modulating the signals, it turns the light green just enough for the chromosomes to latch on. Once this first stable connection is formed, the rest follows naturally: the chromosomes align in the middle, guided by spindle geometry and microtubule dynamics.

“It’s not about brute force,” says Tolić. “It’s about creating the conditions necessary for the system to function properly. The key role of CENP-E is to stabilize the beginning, and once that happens, the rest of mitosis proceeds properly.”

A textbook story unfolds

For almost 20 years, biology textbooks taught the simpler story of CENP-E as a motor protein pulling cargo toward the metaphase plate. The Zagreb study requires a rewriting.

“Congression, the alignment of chromosomes, is intrinsically linked to biorientation,” explains Tolić. “What we show is that CENP-E does not contribute significantly to the movement itself. Its crucial role is to stabilize the final attachments initially. This is what allows the system to proceed correctly.”

This is a fundamental design shift away from force and movement and toward regulation and timing. And this change has consequences far beyond the classroom.

To outsiders, the distinction may seem subtle. In biology, details matter. Errors in chromosome segregation are a defining feature of cancer. Tumor cells are patchworks of duplications and deletions of entire chromosomes or their segments, each traced back to a failure of the cellular trafficking system.

By showing that the primary role of CENP-E is to regulate early attachments and linking this regulation to Aurora kinase activity, the Zagreb team has not only linked two processes once thought to act independently, but mapped a critical vulnerability. This idea could inspire drugs that would fine-tune the balance, suppressing runaway divisions or saving those that have stalled.

“It’s not just about rewriting a model,” says Vukušić. “It’s about identifying a mechanism directly linked to the disease. This opens the door to diagnosis and consideration of new therapies.”

Order in apparent chaos

At its heart, discovery is about finding order in chaos. Every day, billions of cells divide in the human body, each betting against entropy. Zagreb’s work illuminates one of the hidden rules of this game. By redefining the role of CENP-E and linking it to other processes inside cells, the team has given biology a clearer picture of how cells maintain their traffic under impossible pressure.

“By discovering how these microscopic regulators cooperate,” says Tolić, “we not only deepen our understanding of biology, but we also come closer to correcting the failures that cause disease.”