RASSF7 is a member of a new family of RAS association domain-containing proteins and is required for completing mitosis

TY - JOUR

T1 - RASSF7 is a member of a new family of RAS association domain-containing proteins and is required for completing mitosis

AU - Sherwood, Victoria

AU - Manbodh, Ria

AU - Sheppard, Carol

AU - Chalmers, Andrew D.

PY - 2008/4

Y1 - 2008/4

N2 - Mitosis is a fundamental feature of all cellular organisms. It must be tightly regulated to allow normal tissue growth and to prevent cancer formation. Here, we identify a new protein that is required for mitosis. We show that the Ras association (RA) domain-containing protein, RASSF7, is part of an evolutionarily conserved group of four proteins. These are RASSF7, RASSF8, and two new RASSF proteins P-CIP1/RASSF9 and RASSF10. We call this group the N-terminal RASSF family. We analyzed the function of Xenopus RASSF7. RASSF7 was found to be expressed in several embryonic tissues including the skin, eyes, and neural tube. Knocking down its function led to cells failing to form a mitotic spindle and arresting in mitosis. This caused nuclear breakdown, apoptosis, and a striking loss of tissue architecture in the neural tube. Consistent with a role in spindle formation, RASSF7 protein was found to localize to the centrosome. This localization occurred in a microtubule-dependent manner, demonstrating that there is a mutually dependant relationship between RASSF7 localization and spindle formation. Thus RASSF7, the first member of the N-terminal RASSF family to be functionally analyzed, is a centrosome-associated protein required to form a spindle and complete mitosis in the neural tube.

AB - Mitosis is a fundamental feature of all cellular organisms. It must be tightly regulated to allow normal tissue growth and to prevent cancer formation. Here, we identify a new protein that is required for mitosis. We show that the Ras association (RA) domain-containing protein, RASSF7, is part of an evolutionarily conserved group of four proteins. These are RASSF7, RASSF8, and two new RASSF proteins P-CIP1/RASSF9 and RASSF10. We call this group the N-terminal RASSF family. We analyzed the function of Xenopus RASSF7. RASSF7 was found to be expressed in several embryonic tissues including the skin, eyes, and neural tube. Knocking down its function led to cells failing to form a mitotic spindle and arresting in mitosis. This caused nuclear breakdown, apoptosis, and a striking loss of tissue architecture in the neural tube. Consistent with a role in spindle formation, RASSF7 protein was found to localize to the centrosome. This localization occurred in a microtubule-dependent manner, demonstrating that there is a mutually dependant relationship between RASSF7 localization and spindle formation. Thus RASSF7, the first member of the N-terminal RASSF family to be functionally analyzed, is a centrosome-associated protein required to form a spindle and complete mitosis in the neural tube.

KW - Animals

KW - Apoptosis

KW - Base sequence

KW - Centrosome

KW - DNA primers

KW - Drosophila proteins

KW - Evolution, Molecular

KW - Gene expression regulation, Developmental

KW - Gene silencing

KW - Humans

KW - Mitosis

KW - Monomeric GTP-binding proteins

KW - Neural tube defects

KW - Spindle apparatus

KW - Xenopus

KW - Xenopus proteins

U2 - 10.1091/mbc.E07-07-0652

DO - 10.1091/mbc.E07-07-0652

M3 - Article

C2 - 18272789

SN - 1059-1524

VL - 19

SP - 1772

EP - 1782

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

IS - 4

ER -