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Blood, 1 May 2002, Vol. 99, No. 9, pp. 3293-3301
IMMUNOBIOLOGY
Human Immune Associated Nucleotide 1: a member of a new guanosine
triphosphatase family expressed in resting T and B cells
Marie Cambot,
Sandra Aresta,
Brigitte Kahn-Perlès,
Jean de
Gunzburg, and
Paul-Henri Roméo
From the Institut National de la Santé et de la
Recherche Médicale U474, ICGM, Maternité Port-Royal, Paris,
France; Institut National de la Santé et de la Recherche
Médicale U528, Institut Curie-Section Recherche, Paris, France;
and Institut National de la Santé et de la Recherche
Médicale U119, Institut Paoli-Calmettes, Marseilles, France.
TAL-1 is a basic helix-loop-helix oncoprotein that is
expressed in up to 30% of T-cell acute lymphoblastic leukemias but not in the T lineage. We have cloned a complementary DNA, called Human Immune Associated Nucleotide 1 (hIAN1), whose messenger RNA (mRNA) level expression is inversely correlated to the TAL-1 mRNA level in
human leukemic T-cell lines. The hIAN1 encodes a 38-kd protein that belongs to a novel family of proteins conserved from plants to
humans and characterized by motifs related to, but highly divergent from, the consensus motifs found in guanosine triphosphate
(GTP)-binding proteins. Despite these divergent amino acids at
positions involved in GTP/guanosine diphosphate (GDP) binding and
guanosine triphosphatase (GTPase) activities, we found that hIAN1
specifically binds GDP (Kd = 0.47
µM) and GTP (Kd = 6 µM) and
exhibits intrinsic GTPase activity. Among mature hematopoietic cells,
hIAN1 is specifically expressed in resting T and B lymphocytes, and its
expression level tremendously decreased at the protein but not the mRNA
level during B- or T-lymphocyte activation, suggesting a specific
role for this new type of GTPase during the immune response.
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