Journal of Biological Chemistry
Volume 273, Issue 46, 13 November 1998, Pages 30122-30130
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NUCLEIC ACIDS, PROTEIN SYNTHESIS, AND MOLECULAR GENETICS
The Identification of Two Drosophila K Homology Domain Proteins: KEP1 AND SAM ARE MEMBERS OF THE Sam68 FAMILY OF GSG DOMAIN PROTEINS*

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Sam68 is a member of a growing family of RNA-binding proteins that contains an extended K homology (KH) domain embedded in a larger domain called the GSG (GRP33,Sam68, GLD1) domain. To identify GSG domain family members, we searched data bases for expressed sequence tags encoding related portions of the Sam68 KH domain. Here we report the identification of two novel Drosophila KH domain proteins, which we termed KEP1 (KH encompassingprotein) and SAM. SAM bears sequence identity with mammalian Sam68 and may be the Drosophila Sam68 homolog. We demonstrate that SAM, KEP1, and the recently identifiedDrosophila Who/How are RNA-binding proteins that are able to self-associate into homomultimers. The GSG domain of KEP1 and SAM was necessary to mediate the RNA binding and self-association. To elucidate the cellular roles of these proteins, SAM, KEP1, and Who/How were expressed in mammalian and Drosophila S2 cells. KEP1 and Who/How were nuclear and SAM was cytoplasmic. The expression of KEP1 and SAM, but not Who/How, activated apoptotic pathways in Drosophila S2 cells. The identification of KEP1 and SAM implies that a large GSG domain protein family exists and helps redefine the boundaries of the GSG domain. Taken together, our data suggest that KEP1 and SAM may play a role in the activation or regulation of apoptosis and further implicate the GSG domain in RNA binding and oligomerization.

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Supported by grants from the Cancer Research Society and Medical Research Council of Canada; Scholar of the Medical Research Council of Canada.

*

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) AF096272 (SAM) and AF096273 (KEP1).

§

Supported in part by funds from the Gertrude and Charles Clark Cancer Research Fellowship.

Supported by a studentship from the Cancer Research Society.

**

Supported by grants from the National Cancer Institute of Canada (NCIC) and the Cancer Research Society; Research Scientist of the NCIC.