# IMMUNE RESPONSE TO NUCLEAR CONSTITUENTS IN SLE

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 1993 · $181,948

## Abstract

The Ku protein was initially discovered as an autoantigen recognized by
sera from patients with polymyositis-scleroderma overlap syndrome.  It
consists of 70 kDa and 80 kDa subunits and it binds ends of double
stranded DNA.  The present proposal seeks the biological function of the
Ku protein through an effort to identify other proteins with which it
interacts.  Our preliminary studies indicate that one example is the
enzyme DNA-dependent protein kinase (DNA-PK).  this enzyme phosphorylates
several transcription factors including the carboxyl terminal domain of
the large subunit of RNA polymerase II.  these studies will seek to
demonstrate that Ku and DNA-PK assemble into a macromolecular structure
on DNA and they will determine if other proteins participate in this
complex.  Ongoing efforts to define the forms of DNA which are bound by
the Ku heterodimer will be continued.  finally, studies will be carried
out to determine if there is a coordinated expression of autoantibodies
to the various components of the Ku protein-DNA-PK complex in patients
with systemic lupus, scleroderma, and polymyositis.  These studies will
test the hypothesis that Ku protein forms a complex with the 350 kDa
catalytic polypeptide of DNA-PK and directs the latter to appropriate
sites on DNA where phosphorylation of specific transcription factors is
required.  It will also test the hypothesis that in the connective tissue
diseases selected macromolecular structures are targeted for autoimmune
responses with the result that families of autoantibodies are directed
against different components of the targeted structure.  These studies
will lay the foundation for studies which can address how selected "self"
structures come into contact with the immune system, either through
extrusion from cells or from disruption of assembly, transport, or
turnover with the outcome that peptide fragments are inserted into MHC
molecules and expressed on cell surfaces for presentation to the immune
system.

## Key facts

- **NIH application ID:** 3156329
- **Project number:** 2R01AR032549-09
- **Recipient organization:** AUGUSTA UNIVERSITY
- **SAM.gov UEI:** N4WWJC8T2593
- **Principal Investigator:** John A. Hardin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $181,948
- **Award type:** 2
- **Project period:** 1993-07-01 → 1998-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156329

## Citation

> US National Institutes of Health, RePORTER application 3156329, IMMUNE RESPONSE TO NUCLEAR CONSTITUENTS IN SLE (2R01AR032549-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156329. Licensed CC0.

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