The Sp/KLF family contains at least twenty identi® ed members which include Sp1-4 and numerous kruÈppel-like factors. Members of the family bind with varying af® nities to sequences designated asSp1 sites'(eg, GC-boxes, CACCC-boxes, and basic transcription elements). Family members have different transcriptional properties and can modulate each other's activity by a variety of mechanisms. Since cells can express multiple family members, Sp/KLF factors are likely to make up a transcriptional network through which gene expression can be® ne-tuned.Sp1 site'-dependent transcription can be growth-regulated, and the activity, expression, and/or post-translational modi® cation of multiple family members is altered with cell growth. Furthermore, Sp/KLF factors are involved in many growth-related signal transduction pathways and their overexpression can have positive or negative effects on proliferation. In addition to growth control, Sp/KLF factors have been implicated in apoptosis and angiogenesis; thus, the family is involved in several aspects of tumorigenesis. Consistent with a role in cancer, Sp/KLF factors interact with oncogenes and tumor suppressors, they can be oncogenic themselves, and altered expression of family members has been detected in tumors. Effects of changes in Sp/KLF factors are context-dependent and can appear contradictory. Since these factors act within a network, this diversity of effects may arise from differences in the expression pro® le of family members in various cells. Thus, it is likely that the properties of the overall network of Sp/KLF factors play a determining role in regulation of cell growth and tumor progression. J. Cell. Physiol. 188: 143±160, 2001.© 2001 Wiley-Liss, Inc.

Sp1 was the® rst mammalian transcription factor to be cloned (Kadonaga et al., 1987). It binds to GC-rich sequences (eg, Gidoni et al., 1985; Giglioni et al., 1989; Imataka et al., 1992), including GC-boxes, CACCC-boxes (also called GT-boxes) and basic transcription elements (collectively termedSp1 sites' in this review). Early studies indicated that Sp1 was responsible for recruiting TATA-binding protein (Pugh and Tjian, 1991; Zenzie-Gregory et al., 1993) and® xing the transcriptional start site (Blake et al., 1990; Jolliff et al., 1991; Kollmar et al., 1994; Liao et al., 1994; Lu et al., 1994) at TATAA-less promoters. These® ndings, together with the fact thatSp1-sites' are found in the promoters of many housekeeping genes (for review, see Dynan and Tjian, 1985; Black and Azizkhan, 1996), led to the widely held notion that Sp1 acts as a basal transcription factor and thatSp1 sites' represent constitutive promoter elements that support basal transcription at these promoters. However, early studies also showed that Sp1 was subject to extensive post-translational modi®-cation by both glycosylation and phosphorylation (Jackson and Tjian, 1988; Jackson et al., 1990), indicating that its activity was likely to be regulated. The identi® cation of several transcription factors with high homology to Sp1 (Hagen et al., 1992; Kingsley and