Disease relevance of SP3

• The gene cluster including ErbA1 is known to be flanked by the constitutional 15;17 translocation breakpoint in hybrid SP3 and by the acute promyelocytic leukemia (APL) breakpoint, which provides the following gene and breakpoint order: cen-SP3-(D17S33,CRYB1)-NF1-(CSF3,ERBA1, ERBB2)-APL-tel [1].
• The flanking breakpoints of SP3 and API are therefore useful for rapidly localizing new markers to the neurofibromatosis critical region, while the breakpoints of the two translocation patients provide unique opportunities for reverse genetic strategies to clone the NF1 gene [1].
• (3) Serum TPA levels were elevated in 55% of patients with stage I endometrial carcinoma, and serum SP3 levels were elevated in 35% of patients with a stage I malignant ovarian neoplasm and in 45% of patients with endometrial carcinoma [2].
• These results suggest that both Sp1 and Sp3 transcription factor binding to TRE-1 repeat III participate in regulation of HTLV-1 viral gene expression [3].
• Localization of the human SP3 gene to chromosome 7p14-p15.2. The lack of expression in multiple sclerosis does not reflect abnormal gene organization [4].

High impact information on SP3

• We also show that SPR-2 is a nuclear protein and is a member of a protein subfamily that includes human SET, which has been identified in numerous different biochemical assays and at translocation breakpoints associated with a subtype of acute myeloid leukemia [5].
• The SPIRAL1 (SPR1) and SPR2 microtubule-localized proteins and the radial swollen 6 (rsw-6) locus are examples of new molecules and genes that affect both microtubule array organization and cell growth pattern [6].
• We identified PR5 in the CA9 promoter as another SP1/SP3-binding site [7].
• Deficient expression in multiple sclerosis of the inhibitory transcription factor Sp3 in mononuclear blood cells [8].
• In addition, clustered mutation of the SP-conserved motifs of NFATc2 showed that SP1 and SP2, but not SP3, are also important for the inducible transactivation of NFATc2 [9].

Biological context of SP3

• Down-regulation of human type II collagen gene expression by transforming growth factor-beta 1 (TGF-beta 1) in articular chondrocytes involves SP3/SP1 ratio [10].
• Expression of dominant negative Egr-1 and SP3 blocked up-regulation of the ACE promoter by HGF but only reduced up-regulation by PMA [11].
• Human Sp3 transcriptional regulator gene (SP3) maps to chromosome 2q31 [12].
• Human transcription factor Sp3: genomic structure, identification of a processed pseudogene, and transcript analysis [13].
• Functional and binding analysis in the distal promoter region showed that multiple Sp1 elements interacting with a novel Sp3 transcription factor activates the hIGFBP-1 gene promoter [14].

Anatomical context of SP3

• An inhibitory activity of SP3 on the stimulatory effect of SP1 could be confirmed in LRA by contransfection experiments in adipocytes [15].
• Regulation of leukotriene C4 synthase gene expression by SP1 and SP3 in mononuclear phagocytes [16].
• Role of an internal ribosome entry site in the translational control of the human transcription factor Sp3 [17].
• Characterization of the human spr2 promoter: induction after UV irradiation or TPA treatment and regulation during differentiation of cultured primary keratinocytes [18].
• While SPR2 expression was limited to the stratum granulosum (SG) in both normal and transplanted skin retaining the SC, it extended to the stratum spinosum (SS) of the transplanted skin lacking the SC and that of the normal oral mucosa [19].

Associations of SP3 with chemical compounds

• Like Sp1, SPR-1 and SPR-2 contain glutamine and serine/threonine rich amino acid stretches [20].
• Other synthetic polyesters such as poly(trimethylene adipate) (SP3/6), poly(tetramethylene adipate) (SP4/6), and aliphatic-aromatic copolyesters from 1,4-butanediol, terephthalic acid, and adipic acid (BTA-copolymers) exhibit only very low anaerobic microbial susceptibility [21].

Other interactions of SP3

• SPR-2 mRNA is expressed ubiquitously, whereas SPR-1 transcripts are abundant in the brain but barely detectable in other organs [20].
• SP3 acts as a positive regulator on the core promoter of human ZPK gene [22].
• SP3 (135-157 msec) and SP6 (282-339 msec) are probably generated by neurons involved in noxious somatosensation [23].
• In transiently transfected Drosophila SL2 cells, both SP1 and SP3 transactivated the SLC19A3 minimal promoter in a dose-dependent manner and in combination demonstrated an additive stimulatory effect [24].
• We describe that the -66 polymorphism modifies the binding affinity for the SP1/SP3 transcription factors, the -156 polymorphism is included in a yet uncharacterized RUNX2 binding site, and the -443 polymorphism causes differential binding of an unknown factor [25].

Analytical, diagnostic and therapeutic context of SP3

• Electrophoretic mobility shift assays demonstrated the specific interaction of NF-kappaB factors with the NF-kappaB element as well as specific binding of SP1 and SP3 to the SP1 binding site [26].
• In one of these patients, SP3 antibodies were additionally found by IIF and by ELISA (double positive) [27].
• By Western blotting, it identifies the TGase1 protein band only weakly, but recognizes strongly a group of bands of 15-20 kDa, two of which by amino acid analysis and amino acid sequencing are the small proline-rich (SPR) 1 and SPR2 proteins, also expressed in epidermal and epithelial tissues [28].

References