Reference: Boddy MN, et al. (1996) 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 13(5):971-82

Reference Help

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.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, P.H.S.
Authors
Boddy MN, Howe K, Etkin LD, Solomon E, Freemont PS
Primary Lit For
Additional Lit For
Review For

Gene Ontology Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene/Complex Qualifier Gene Ontology Term Aspect Annotation Extension Evidence Method Source Assigned On Reference

Phenotype Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Disease Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Disease Ontology Term Qualifier Evidence Method Source Assigned On Reference

Regulation Annotations


Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, SPELL, or YeastMine.

Regulator Target Direction Regulation Of Happens During Method Evidence

Post-translational Modifications


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Site Modification Modifier Reference

Interaction Annotations


Genetic Interactions

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Assay Annotation Action Modification Source Reference

Functional Complementation Annotations


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Species Gene ID Strain background Direction Details Source Reference