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Molecular cloning and characterization of a novel zinc finger protein: brain expressed ring finger protein (BERP)

University of British Columbia

A novel mammalian RING finger protein which is highly expressed in the brain (Brain expressed RING protein; BERP) was discovered. RING finger proteins are a new family of zinc finger proteins which are involved in processes that regulate cell cycle, growth and differentiation. BERP belongs to a subgroup of RING finger proteins known as the "RING finger-B-box-Coiled Coil (RBCC) proteins. Several RBCC proteins were identified as oncogenes. The human BERP gene mapped to chromosome 1 lpl5, an area containing several tumor suppressor genes. Northern blotting and in situ hybridization analysis indicated that BERP is expressed in all brain regions examined. Immunohistochemical analysis showed that BERP is expressed in several neuronal populations throughout the brain with a punctate pattern in the soma and dendrites. In addition, transiently expressed BERP in human embryonic kidney (HEK) cells is found in the cytoplasm with a punctate distribution. However, the expression of a truncated form of BERP which contains only the N-terminal RBCC domain was found in the nucleus. These results suggest that the C-terminal region of BERP may interact with cytoplasmic proteins while the N-terminus may mediate signals in the nucleus. The yeast two-hybrid assay was used to identify proteins which might interact with BERP. An unconventional class V myosin, interacted with the C-terminus of BERP in yeast and co-immunoprecipitated with BERP. Type V myosins have been implicated in vesicular transport. These data suggest that BERP associates with class V unconventinal myosins and may be involved in vesicular transport. Pheochromocytoma (PC 12) cells transfected with the N-terminus RBCC domain of BERP did not differentiate following nerve growth factor (NGF) treatment while cells expressing the full-length protein responded to NGF treatment and developed neurites. Hence, expression of the truncated BERP may act as a dominant negative mutant of endogenous BERP and block its in vivo functions. The suggested involvement of BERP in neuronal differentiation is consistent with the role of class V myosins in transporting vesicles to sites of filopodial growth. In conclusion, I have discovered a novel RING finger protein, BERP, which may be required for vesicular transport fostering the differentiation and maintenance of neuronal cells.

Thesis/Dissertation

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2009-04-03

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http://hdl.handle.net/2429/6765

Neuroscience

University of British Columbia

UBCV

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