KAP-1, a novel corepressor for the highly-conserved KRAB repression domain.

Format:

Book

Thesis/Dissertation

Author/Creator:

Friedman, Josh Richard.

Contributor:

Rauscher, Frank J., III, advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Molecular biology.

0307.

Penn dissertations--Cell and molecular biology.

Cell and molecular biology--Penn dissertations.

Local Subjects:

Penn dissertations--Cell and molecular biology.

Cell and molecular biology--Penn dissertations.

0307.

Physical Description:

161 pages

Contained In:

Dissertation Abstracts International 57-11B.

System Details:

Mode of access: World Wide Web.

text file

Summary:

The Kruppel-associated box (KRAB) is a conserved, 75 amino acid region found exclusively in Kruppel-type zinc finger proteins (ZFPs). We have shown that the KRAB domain is a DNA-binding-dependent repression domain, and we have identified conserved residues within the KRAB domain that are required for repression. In an effort to determine the mechanism of repression by the KRAB domain, we have purified and cloned KAP-1, a KRAB domain-binding protein. The N-terminus of KAP-1 includes a RING finger motif followed by two B boxes and a region predicted to form a coiled-coil structure; the C-terminus contains a PHD finger and a segment with weak homology to the bromodomain. KAP-1 interacts with KRAB domains derived from several proteins but not with mutant KRAB domains which lack repression activity. Furthermore, exogenous KAP-1 potentiates KRAB domain-mediated repression, and KAP-1 is itself a repressor when fused to a heterologous DNA-binding domain. We conclude that KAP-1 is a corepressor for KRAB domain-mediated repression. In addition, a structure-function analysis of KAP-1 was performed which identifies the KAP-1 RING-B1-B2-coiled-coil as the KRAB interaction domain, and mutations in the RING finger or B2 box were found to eliminate this interaction. Finally, a region of KAP-1 that includes the PHD finger was shown to repress transcription as a GAL4 fusion protein; this repression was lost upon mutation of conserved residues within the PHD finger. Thus, the identification of KAP-1 provides a unifying paradigm for repression by KRAB-ZFPs, and the analysis of KRAB domain-binding and repression by KAP-1 has shed light on the functions of conserved domains found in many other proteins.

Notes:

Thesis (Ph.D. in Cell and Molecular Biology) -- University of Pennsylvania, 1996.

Source: Dissertation Abstracts International, Volume: 57-11, Section: B, page: 6751.

Supervisor: Frank J. Rauscher, III.

Local Notes:

School code: 0175.

ISBN:

9780591204766

Access Restriction:

Restricted for use by site license.