Poster Presentation 25th Lorne Cancer Conference 2013

Investigating the function of the novel nuclear protein Manp. (#103)

James Allen 1 , Louise Winteringham 1 , Charlie Bond 2
  1. Western Australia Institute for Medical Research, Perth, WA, Australia
  2. School of Biochemistry, University of Western Australia, Perth, Western Australia, Australia

Mlf1-associated-nuclear-protein (Manp), also known as hnrnpul2, is a recently identified chromatin binding protein. We first characterised Manp by its ability to interact with the transcriptional regulator Myeloid leukemia factor 1 (Mlf1). Importantly, Manp can affect the subcellular localisation of Mlf1 promoting its translocation from the cytoplasm to the nucleus1 . Mlf1 functions to promote myeloid lineage commitment while preventing terminal erythroid differentiation2 . Recently, the involvement of Manp in the cellular response to double stranded DNA breakages was reported3 .

Manp shares significant sequence similarity with hnRNP-U. Both proteins share conserved DNA binding domains, as well as  putative ATPase/kinase features. Manp differs from hnRNP-U in that it lacks RNA binding features present in hnRNP-U.

A yeast 2-hybrid assay and subsequent co-immunoprecipitation identified Topoisomerase II alpha as a binding partner of Manp. Topoisomerase II is an enzyme that regulates the topological state of DNA during various cellular processes including transcription, replication and mitotic chromosomal segregation. We have investigated the role of Manp in regulating the activity of Topoisomerase II. While our data did not demonstrate that Manp could alter Topoisomerase II catalytic activity, ectopic Manp expression did confer resistance to the Topoisomerase II poison etoposide.

These results will be presented.

  1. J Biol Chem. 2006 Dec 15;281(50):38791-800.
  2. EMBO J. 1999 Oct 15;18(20):5559-66.
  3. Mol Cell. 2012 Feb 24;45(4):505-16.