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Functional characterization of multiple domains involved in the subcellular localization of the hematopoietic Pbx interacting protein (HPIP)

Oncogene volume 21, pages 6766–6771 (2002)Cite this article

Abstract

We have previously reported the cloning of the Hematopoietic Pbx Interacting Protein (HPIP), a novel protein discovered through its interaction with Pbx1. HPIP is expressed in early hematopoietic precursors, can bind all members of the Pbx family and can inhibit the transcriptional activation of the oncogene E2A-Pbx. To further understand the function of HPIP, we have analysed its cellular localization and characterized its functional localization domains. Using fluorescence microscopy to follow the distribution of different HPIP sequences fused to GFP, we found that HPIP localizes predominantly to cytoskeletal fibers but has the potential ability to shuttle between the nucleus and the cytosol. The cytoskeletal localization of HPIP is mediated by an N-terminal leucine rich region (between aa 190–218) and can be disrupted by the microtubule destabilizing drug vincristine. The HPIP C-terminal domain (aa 443–731) bears a nuclear export activity that is blocked by the CRM1 inhibitor Leptomycin B. In addition, we found two basic amino acid regions located between aa 485–505 and aa 695–720 that contain nuclear import activities attenuated by nuclear export. These observations support a model in which the constitutive attachment of HPIP to the cytoskeleton could be modified by changes in functional domains implicated in nuclear export, import and cytoskeleton binding sequences, allowing the molecule to shuttle between the nucleus and the cytosol.

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Acknowledgements

This work was supported by the National Cancer Institute of Canada with funds from the Canadian Cancer Society and the Terry Fox Foundation; and the National Institute of Health (Grant Number HL65430). C Abramovich was the recipient of fellowships from the Leukemia Research Society of Canada and the Canadian Institutes for Health Research. We thank Ian Waissbluth for his technical assistance and Drs Minoru Yoshida (Tokyo University, Japan) and Tom Hope (Salk Institute for Biological Studies, La Jolla, CA, USA) for kindly providing LMB.

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Authors and Affiliations

  1. Terry Fox Laboratory, British Columbia Cancer Agency, 601 West 10th Avenue, Vancouver, V5Z 1L3, BC, Canada

    Carolina Abramovich, Elizabeth A Chavez, Peter M Lansdorp & R Keith Humphries

  2. Department of Medicine, University of British Columbia, Vancouver, V6T 2B5, BC, Canada

    Peter M Lansdorp & R Keith Humphries

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  1. Carolina Abramovich
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  2. Elizabeth A Chavez
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  3. Peter M Lansdorp
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  4. R Keith Humphries
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Correspondence to R Keith Humphries.

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Abramovich, C., Chavez, E., Lansdorp, P. et al. Functional characterization of multiple domains involved in the subcellular localization of the hematopoietic Pbx interacting protein (HPIP). Oncogene 21, 6766–6771 (2002). https://doi.org/10.1038/sj.onc.1205784

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