التفاصيل البيبلوغرافية
| العنوان: |
Progressive Purkinje Cell Degeneration in tambaleante Mutant Mice Is a Consequence of a Missense Mutation in |
| المؤلفون: |
Herc E, Ubiquitin Ligase, Tomoji Mashimo, Ouadah Hadjebi, Fabiola Amair-pinedo, Toshiko Tsurumi, Francina Langa, Tadao Serikawa, Constantino Sotelo, Jean-louis Guénet, Jose Luis Rosa |
| المساهمون: |
The Pennsylvania State University CiteSeerX Archives |
| المصدر: |
ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/d5/02/PLoS_Genet_2009_Dec_24_5(12)_e1000784.tar.gz |
| المجموعة: |
CiteSeerX |
| الوصف: |
The HERC gene family encodes proteins with two characteristic domains: HECT and RCC1-like. Proteins with HECT domains have been described to function as ubiquitin ligases, and those that contain RCC1-like domains have been reported to function as GTPases regulators. These two activities are essential in a number of important cellular processes such as cell cycle, cell signaling, and membrane trafficking. Mutations affecting these domains have been found associated with retinitis pigmentosa, amyotrophic lateral sclerosis, and cancer. In humans, six HERC genes have been reported which encode two subgroups of HERC proteins: large (HERC1-2) and small (HERC3-6). The giant HERC1 protein was the first to be identified. It has been involved in membrane trafficking and cell proliferation/growth through its interactions with clathrin, M2-pyruvate kinase, and TSC2 proteins. Mutations affecting other members of the HERC family have been found to be associated with sterility and growth retardation. Here, we report the characterization of a recessive mutation named tambaleante, which causes progressive Purkinje cell degeneration leading to severe ataxia with reduced growth and lifespan in homozygous mice aged over two months. We mapped this mutation in mouse chromosome 9 and then performed positional cloning. We found a GuA transition at position 1448, causing a Gly to Glu substitution (Gly483Glu) in the highly conserved N-terminal RCC1-like domain of the HERC1 protein. Successful transgenic rescue, with either a mouse BAC containing the normal copy of Herc1 or with the human HERC1 cDNA, validated our findings. Histological and biochemical studies revealed |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/zip |
| اللغة: |
English |
| Relation: |
http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.356.3725 |
| الاتاحة: |
http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.356.3725 |
| Rights: |
Metadata may be used without restrictions as long as the oai identifier remains attached to it. |
| رقم الانضمام: |
edsbas.F00C0CD9 |
| قاعدة البيانات: |
BASE |