Identification and Characterization of a Leukocyte-specific Component of the Nuclear Body

doi:10.1074/jbc.271.46.29198

Identification and Characterization of a Leukocyte-specific Component of the Nuclear Body*

From the Department of Medicine, Harvard Medical School and the ^‡ Arthritis Unit,
^¶ Cardiovascular Research Center
^∥ Division of Neuropathology, Cancer Center, of the General Medical Services, Massachusetts General Hospital, Boston, Massachusetts 02129

^§To whom correspondence should be addressed:
Massachusetts General Hospital-East, CNY-8, 149 13th St., Charlestown, MA 02129
. Tel.: 617-726-3780; Fax: 617-726-5651; E-mail: bloch{at}helix.mgh.harvard.edu .

Abstract

The nuclear body (NB) is a cellular organelle that is involved in the pathogenesis of acute promyelocytic leukemia and viral infection. The NB is also a target of antibodies in the serum of patients with the autoimmune disease primary biliary cirrhosis. In this study, serum from a patient with primary biliary cirrhosis was used to identify a cDNA encoding a novel component of the NB, a 140-kDa protein designated Sp140. The predicted amino acid sequence of the amino-terminal portion of Sp140 was similar to Sp100, a previously identified NB protein. The carboxyl portion of Sp140 contained a zinc-finger domain and a bromodomain, motifs that are present in proteins regulating gene transcription. High levels of Sp140 mRNA were detected in human spleen and peripheral blood leukocytes, but not other human tissues. The level of SP140 mRNA in myeloid precursor cell lines HL60 and NB4 markedly increased in response to chemically induced cellular differentiation. Immunohistochemical techniques were used to demonstrate that SP140 localized to the NB in differentiated HL60 and NB4 cells. The location of Sp140 in the NB, and expression of this gene in cells involved in host defense, suggest that Sp140 may be involved in the pathogenesis of acute promyelocytic leukemia and viral infection.

Footnotes

↵* This work was supported in part by United States Public Health Service Grants AR01866 and DK51179 (to D. B. B.), HL45895 (to K. D. B.), and NS29793 (to S. M. d. l. M.), by grants from the Sjögren's Syndrome Foundation, Inc., and Arthritis Foundation (to D. B. B.), and by a grant to the Cardiovascular Research Center from Bristol-Myers Squibb Pharmaceuticals. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) U63420[GenBank]
↵¹ The abbreviations used are:

NB

nuclear body

APL

acute promyelocytic leukemia

5′-RACE

rapid amplification of cDNA 5′ ends

GST

glutathione S-transferase

HUVEC

human umbilical vein endothelial cells

IFN

interferon

ORF

open reading frame

PBC

primary biliary cirrhosis

RA

all-trans retinoic acid

RAR-α

retinoic acid receptor-α

ABC

avidin-biotin complexes

PMA

phorbol 12-myristate 13-acetate

DAB

3,3′-diaminobenzimide

bp

base pair(s).
- Received March 28, 1996.
- Revision received July 30, 1996.