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PIC 1, a novel ubiquitin-like protein which interacts with the PML component of a multiprotein complex that is disrupted in acute promyelocytic leukaemia

Academic Article
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Overview

authors

  • Boddy, Michael
  • Howe, K.
  • Etkin, L. D.
  • Solomon, E.
  • Freemont, P. S.

publication date

  • September 1996

journal

  • Oncogene  Journal

abstract

  • Acute promyelocytic leukaemia (APL) arises following a reciprocal translocation t(15;17) that fuses PML with retinoic acid receptor alpha (RARA). The PML-RARA fusion protein targets and disrupts nuclear multiprotein complexes called PODs, ND10 or NBs, a process which is associated with a block in myeloid differentiation leading to APL. A human B-cell cDNA library was screened for PML-interacting clones and a single positive clone (PIC1) was isolated. The sequence of PIC1 shows 52% identity to a S. cerevisiae ubiquitin-like protein that was cloned as a suppressor of mutations in MIF2, a protein required for mitotic spindle integrity during anaphase. Transient transfection of NIH3T3 cells with PIC1 results in a nuclear staining pattern coincident with that of endogenous mouse PML. Further, cotransfection of PIC1 with human PML produces a completely overlapping staining pattern between the two proteins. An antibody raised against PIC1 detects a punctate staining pattern in HeLa cells that is coincident with endogenous human PML. There is no significant colocalisation observed between the staining of PML/ PML-RARA and PIC1 in an APL-derived cell line NB4, as compared to cells expressing only wild type PML. However, following all trans retinoic acid treatment of NB4 cells a significant relocalisation of PIC1 and PML is observed. PIC1 is the first identified NB-associated protein that interacts with PML, the function of which may lead to a fuller understanding of the molecular events leading to APL.

subject areas

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Cell Line
  • Clone Cells
  • Cloning, Molecular
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Escherichia coli
  • Fluorescent Antibody Technique, Indirect
  • HeLa Cells
  • Humans
  • Hybrid Cells
  • Lamins
  • Leukemia, Promyelocytic, Acute
  • Mice
  • Molecular Sequence Data
  • Neoplasm Proteins
  • Nuclear Proteins
  • Protein Biosynthesis
  • Recombinant Fusion Proteins
  • SUMO-1 Protein
  • Saccharomyces cerevisiae
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Tissue Distribution
  • Transcription Factors
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins
  • Ubiquitins
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Research

keywords

  • APL
  • PML
  • interacting clone
  • ubiquitin-like
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Identity

International Standard Serial Number (ISSN)

  • 0950-9232

PubMed ID

  • 8806687
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Additional Document Info

start page

  • 971

end page

  • 982

volume

  • 13

issue

  • 5

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