Volume 272, Number 6, Issue of February 7, 1997 pp. 3129-3132
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

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COMMUNICATION:
A Role for Sam68 in Cell Cycle Progression Antagonized by a Spliced Variant within the KH Domain

(Received for publication, October 10, 1996, and in revised form, December 3, 1996)

From the Gene Medicine Department, Rhône-Poulenc Rorer, 13 Quai Jules Guesde, 94403 Vitry sur Seine, Cedex, France

Sam68 is the main tyrosine-phosphorylated and Src-associated protein in mitotic cells. Sam68 exhibits a conserved functional KH (hnRNPK homology) RNA binding domain and binds single strand nucleic acids. Tyrosine phosphorylation mediates the interaction of Sam68 with many SH3- and SH2-containing proteins and negatively regulates its nucleic acid binding properties. But the function and the impact of Sam68 on cell signaling and cell proliferation remains elusive. We report here the identification of a natural isoform of Sam68 with a deletion within the KH domain. This isoform, called Sam68KH, is specifically expressed at growth arrest upon confluency in normal cells. In cells that do not enter quiescence at confluency such as Src-transformed cells, no recruitment of Sam68KH is observed. Transfected Sam68KH inhibits serum-induced DNA synthesis and cyclin D1 expression. Sam68 overcomes these effects, suggesting that isoforms of Sam68 are involved, through KH domain signaling, in cell proliferation, and more precisely in G₁/S transition.

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