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J. Biol. Chem., Vol. 281, Issue 50, 38791-38800, December 15, 2006

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Myeloid Leukemia Factor 1 Associates with a Novel Heterogeneous Nuclear Ribonucleoprotein U-like Molecule^*

From the Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Perth, Western Australia 6000, Australia

Myeloid leukemia factor 1 (MLF1) is an oncoprotein associated with hemopoietic lineage commitment and acute myeloid leukemia. Here we show that Mlf1 associated with a novel binding partner, Mlf1-associated nuclear protein (Manp), a new heterogenous nuclear ribonucleoprotein (hnRNP) family member, related to hnRNP-U. Manp localized exclusively in the nucleus and could redirect Mlf1 from the cytoplasm into the nucleus. The nuclear content of Mlf1 was also regulated by 14-3-3 binding to a canonical 14-3-3 binding motif within the N terminus of Mlf1. Significantly Mlf1 contains a functional nuclear export signal and localized primarily to the nuclei of hemopoietic cells. Mlf1 was capable of binding DNA, and microarray analysis revealed that it affected the expression of several genes, including transcription factors. In summary, this study reveals that Mlf1 translocates between nucleus and cytoplasm, associates with a novel hnRNP, and influences gene expression.

Received for publication, June 6, 2006 , and in revised form, September 18, 2006.

The nucleotide sequence(s) reported in this paper has been submitted to the Gen-Bank TM/EBI Data Bank with accession number(s) DQ000354 [GenBank] .

The amino acid sequence of this protein can be accessed through NCBI Protein Database under NCBI accession number AAY44301 [GenBank] .

^* This work was supported in part by grants from the National Health and Medical Research Council (Grant 254668 to S. P. K.), The Cancer Council Western Australia, and The Medical Research Foundation Royal Perth Hospital. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Present address: Dept. of Developmental Neurobiology, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794.

² Recipient of an Australian Rotary Health and Research Fund Scholarship.

³ To whom correspondence should be addressed: Laboratory for Cancer Medicine, Western Australian Inst. for Medical Research, Perth, WA 6000, Australia. Tel.: 61-8-92240334; Fax: 61-8-92240322; E-mail: pklinken{at}waimr.uwa.edu.au.

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