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Functional regulation of pre-B-cell leukemia homeobox interacting protein 1 (PBXIP1/HPIP) in erythroid

Bramanandam Manavathi1, Dennis Lo, Suresh Bugide

  • 1Molecular and Cellular Oncology Laboratory, Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad-500046, India. manavathibsl@uohyd.ernet.in

The Journal of Biological Chemistry
|December 22, 2011
PubMed

Insights

Human PBX1 interacting protein (HPIP) promotes hematopoietic colony formation and erythroid differentiation by activating the PI3K/AKT pathway. HPIP is a target of GATA1 and CTCF, playing a key role in erythroid cell development.

Area of Science:

  • Hematopoiesis and Cell Differentiation
  • Molecular Biology and Gene Regulation

Background:

  • Human PBX1 interacting protein (HPIP) is a co-repressor of PBX1 and regulates estrogen receptor functions.
  • The role of HPIP in hematopoiesis, particularly erythroid differentiation, remains largely unexplored despite its initial discovery in hematopoietic cells.

Purpose of the Study:

  • To investigate the function of HPIP in hematopoiesis and erythroid differentiation.
  • To elucidate the molecular mechanisms underlying HPIP's effects on hematopoietic cells, including the involvement of the PI3K/AKT pathway and transcription factors.

Main Methods:

  • Overexpression and knockdown of HPIP in human CD34(+) cells and K562 leukemia cell line.
  • Assessment of hematopoietic colony formation in vitro and erythroid differentiation.
  • Analysis of the PI3K/AKT pathway activation using a specific inhibitor (LY-294002).
  • Investigation of HPIP gene regulation by GATA1 and CTCF using promoter binding assays, co-immunoprecipitation, and co-localization studies.

Main Results:

  • HPIP overexpression enhanced hematopoietic colony formation and erythroid differentiation in CD34(+) cells and K562 cells.
  • HPIP overexpression activated the PI3K/AKT pathway, which was crucial for its effects on cell growth and differentiation.
  • HPIP gene expression is induced by erythroid differentiation signals and regulated by the transcription factors GATA1 and CTCF.

Conclusions:

  • HPIP plays a significant role in promoting hematopoietic progenitor growth and erythroid differentiation.
  • The PI3K/AKT pathway mediates HPIP's functional effects on hematopoietic cells.
  • HPIP is identified as a direct transcriptional target of GATA1 and CTCF in erythroid cells, highlighting its integration into erythroid lineage-specific gene regulatory networks.

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