Protein family review

This in an extract of a protein family review which first appeared in GenomeBiology, and is reproduced by permission of the publisher, BioMedCentral Ltd.

Authors:

Joanna Kaczynski^1 ,2 , Tiffany Cook⁴ and Raul Urrutia^1 ,2 ,3

¹Gastroenterology Research Unit, Mayo Clinic, Rochester, MN 55901, USA
²Tumor Biology Program, Mayo Clinic, Rochester, MN 55901, USA
³Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55901, USA
⁴Department of Biology, New York University, New York, NY 10003, USA

Correspondence:

Raul Urrutia.

Email:

urrutia.raul@mayo.edu

Read the full article

Subscribers to GenomeBiology may view the full version of this review article online at genomebiology.com/

Published:

3 February 2003

Sp1- and Krüppel-like transcription factors

Summary

Sp1-like proteins and Krüppel-like factors (KLFs) are highly related zinc-finger proteins that are important components of the eukaryotic cellular transcriptional machinery. By regulating the expression of a large number of genes that have GC-rich promoters, Sp1-like/KLF transcription regulators may take part in virtually all facets of cellular function, including cell proliferation, apoptosis, differentiation, and neoplastic transformation. Individual members of the Sp1-like/KLF family can function as activators or repressors depending on which promoter they bind and the coregulators with which they interact. A long-standing research aim has been to define the mechanisms by which Sp1-like factors and KLFs regulate gene expression and cellular function in a cell- and promoter-specific manner. Most members of this family have been identified in mammals, with at least 21 Sp1-like/KLF proteins encoded in the human genome, and members are also found in frogs, worms and flies. Sp1-like/KLF proteins have highly conserved carboxy-terminal zinc-finger domains that function in DNA binding. The amino terminus, containing the transcription activation domain, can vary significantly between family members.

Frontiers

Several lines of investigation are needed to further our understanding of how the many members of the Sp1-like/KLF protein family regulate gene expression in a promoter-, cell-, and tissue-specific manner; whether they antagonize each other's functions to fine-tune specific cellular processes; and whether they participate in a hierarchical cascade of gene expression. The identification of the structural features that correlate with either similarities or differences between family members are necessary not only for better understanding of the biochemistry of Sp1-like/KLF proteins but also for a theoretical framework to be constructed for use in the development of specific small-molecule antagonists, which can be used to manipulate Sp1-like/KLF proteins both in vitro and in vivo.

Another important area of research pertains to the transcriptional regulatory function of the amino-terminal domains of these proteins. What are the molecular mechanisms that regulate how these domains interact with coregulatory complexes and thereby repress or activate gene expression? Further insights into the functions of different Sp1-like/KLF proteins have the potential to change the partially informative classification of these proteins, which is currently based on primary structure. Lastly, because these proteins are important in morphogenesis, it is likely that they may play a significant role in the mechanisms underlying human diseases that are characterized by aberrant growth and differentiation, such as cancer. Future studies of the Sp1-like/KLF proteins have a large potential for defining the machinery that not only regulates physiological processes but may also modulate human diseases.

Mammalian members of the Sp1-like/KLF family

Structural properties of Sp1-like/KLF proteins