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

Oncogene. 1996 Sep 5;13(5):971-82.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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


  • CDKN1A protein, human
  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Lamins
  • Neoplasm Proteins
  • Nuclear Proteins
  • Pml protein, mouse
  • Promyelocytic Leukemia Protein
  • Recombinant Fusion Proteins
  • SUMO-1 Protein
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Ubiquitins
  • PML protein, human

Associated data

  • GENBANK/U61397