Millennium Pharmaceuticals Limited

Millennium Biotherapeutics, Inc.

Steven Bossone

Sean Anthony McCarthy

Christine Ellen Bulawa

Michael Joseph Kuranda

The invention involves a method of identifying nucleic acid sequences encoding signal peptide-containing proteins. The method features chimeric constructs containing a KRE9 gene that lacks a signal sequence. Yeast containing chimeric KRE9 plasmid constructs that encode signal sequences are selected based on their ability to grow on media in which sucrose is the sole carbon source.

Genes encoding polypeptides containing signal sequences

The invention provides isolated nucleic acid molecules, designated TANGO 281, which encode proteins downregulated in megakaryocytes that fail to express the gata-1 transcription factor (a factor critical for blood cell formulation) and can, therefore, represent direct or indirect gata-1 targets. The invention also provides antisense nucleic acid molecules, expression vectors containing the nucleic acid molecules of the invention, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a nucleic acid molecule of the invention has been introduced or disrupted. The invention still further provides isolated polypeptides, fusion polypeptides, antigenic polypeptides and antibodies. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.

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Lexington, MA, United States of America

Steven Bossone