HUNTSMAN CANCER INSTITUTE
UNIVERSITY OF UTAH

September 8, 2003
HCI Researchers Identify Key Mechanism to Cell Division
Discovery may lead to understanding rapid cell division in cancer

September 8, 2003 — Science is a step closer to unlocking one of the mysteries of life — how one cell, through a process of division and multiplication, becomes many cells. In a report published today in Developmental Cell, Huntsman Cancer Institute researchers reveal new insight into the mechanics and regulation involved in dividing the nucleus during the cell cycle. This step may be especially important to rapidly dividing cells like those that lead to cancer.

During the cell division cycle, many activities must take place at specific points in the cycle: DNA is replicated, chromosomes are condensed, and the membrane that separates the cell’s nucleus from the cytoplasm, called the nuclear envelope, must dissolve. This disassembly is key to the accurate inheritance of genetic material.

Katharine Ullman, PhD, Huntsman Cancer Institute investigator and leader of the team that made the discovery, reports an unexpected role for a nuclear pore protein called Nup153 in reorganizing the cell’s nucleus prior to division, or mitosis. Nuclear pore complexes are specialized portals in the nuclear envelope. In any given cell, there are typically thousands of such pores. Each acts as a tightly regulated gateway, allowing only certain proteins either entry or exit from the nucleus. Nup153 is a pore protein involved in this regulatory process. However, in this study Ullman and HCI co-authors Jin Liu, PhD, Amy Prunuske, and Ammon Fager discovered that Nup153 has an unconventional role in directing a group of proteins known as coatomer protein complex1 (COP1) to the nuclear membrane at a specific time in the cell cycle, when a cell is undergoing mitosis. Ullman explains that the lab used a system where nuclei were formed in a test tube and then triggered to enter mitosis. When the researchers manipulated the function of either Nup153 or the COP1 complex, disassembly of the nuclear envelope was dramatically impaired.

According to Ullman, this data suggests that a process called vesiculation, currently thought to be unnecessary for nuclear envelope breakdown, is in fact important for the nuclear envelope to dissolve. "What was known before we obtained our results is that some cellular processes, namely those involved with a part of the cell known as the Golgi apparatus, were essential in the reassembly of the nuclear envelope," Ullman says. "What wasn’t appreciated was that a different set of cellular machinery, also localized to the Golgi, plays a role in nuclear disassembly."

The researchers are looking forward to further studies into the role of COP1 and Nup153 in cell mitosis. "In a rapid cell cycle, any mechanism that contributes to quick dissolution of the nuclear envelope could be important to allow a cell to proliferate quickly," Ullman says. "Understanding cell cycle control is fundamental to understanding how to interfere with tumor cell growth."

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