Disease relevance of ZBTB7A

• We find that FBI-1 binds to inverted sequence repeats downstream of the HIV-1 transcription start site [1].
• Indeed, FBI-1 binding sites in the adenovirus 2 major late promoter, the c-fos gene, and the c-myc P1 and P2 promoters reveal variously spaced direct, inverted, and everted sequence repeats with the consensus sequence G(A/G)GGG(T/C)(C/T)(T/C)(C/T) for each repeat [1].
• In this study, a yeast one-hybrid screen for proteins that associate with the NRE led to the identification of the leukemia/lymphoma-related factor (LRF), a transcriptional repressor that contains a POZ (poxvirus zinc finger) domain, as an NRE-binding protein [2].
• Purification and characterization of FBI-1, a cellular factor that binds to the human immunodeficiency virus type 1 inducer of short transcripts [3].
• Low per cent responses to LRF were seen primarily in patients with pituitary disease, a situation most clearly delineated by blood FSH measurements [4].
• FBI-1 is aberrantly overexpressed in many human solid tumors, particularly in adenocarcinomas and squamous carcinomas [5].

Psychiatry related information on ZBTB7A

• The constellation of normal quantitative but abnormal kinetic LRF and TRF responses supports the hypothesis that the endocrine changes seen in anorexia nervosa are consistent with hypothalamic dysfunction [6].

High impact information on ZBTB7A

• Since a short luteal phase is associated with an endometrium not conductive to implantation, administration of the LRF agonist at the onset of menstrual cycle may prove to be a practical and novel approach to fertility control [7].
• Subcutaneous injection of 50 micrograms of a luteinizing hormone-releasing factor agonist (LRF agonist) for three successive days at the time of menstruation in normal cycling women induces a shortened luteal phase with suboptimal concentrations of circulating estradiol and progesterone [7].
• The elevated LH levels appeared to be related to a heightened pituitary responsiveness to the LRF [8].
• These tests included (a) the pulsatile pattern and day-to-day fluctuation of gonadotropin release; (b) effects of exogenous estrogen and antiestrogen (clomiphene) administration on gonadotropin release; and (c) pituitary responsiveness to maximal (150 mug) and submaximal (10 mug) luteinizing hormone-releasing factor (LRF) injections [8].
• The present study demonstrates the pituitary component of the estrogen-induced changes in the sensitivity to LRF [9].

Chemical compound and disease context of ZBTB7A

• The immunoperoxidase technique was used to identify LRF and glycoprotein hormones or their subunits in 22 carcinoid tumors of various origins [10].
• In the 2 boys with CAH, the one with the more advanced bone age, 11-6/12 yr, developed true precocious puberty following initiation of cortisone treatment and had a pubertal LRF-evoked LH release on 3 occasions; the more immature boy, bone age 10, had a prepubertal LH rise [11].
• The mean concentration of plasma estradiol rose significantly above resting levels after LRF in the girls with idiopathic precocious puberty [12].
• Five infertile males, ages 25 to 35, with oligospermia and varicocele had following gonadotropin-releasing hormone (LRF) infusion a rise of serum follicle-stimulating hormone, luteinizing hormone, and testosterone levels which was not different from that of normal fertile males [13].

Biological context of ZBTB7A

• Novel BTB/POZ domain zinc-finger protein, LRF, is a potential target of the LAZ-3/BCL-6 oncogene [14].
• At approximately 9.5-10.0 days of embryonic development, the mouse LRF gene was expressed in the limb buds, pharyngeal arches, tail bud, placenta and neural tube [14].
• We have used various viral and cellular FBI-1 binding sites to characterize the interaction of a POZ-domain protein with DNA in detail [1].
• Role of the POZ zinc finger transcription factor FBI-1 in human and murine adipogenesis [15].
• We found that a POZ domain protein, factor that binds to inducer of short transcripts-1 (FBI-1), was induced during both murine and human preadipocyte differentiation with maximal expression levels seen at days 2-4 [15].

Anatomical context of ZBTB7A

• Both human and mouse LRF genes, which localized to syntenic chromosomal regions (19p13.3 and 10B5.3, respectively), were widely expressed in adult tissues and cell lines [14].
• FBI-1 mRNA was expressed in human adipose tissue with the highest levels found in samples from morbidly obese subjects [15].
• FBI-1 enhanced NF-kappaB-mediated transcription of E-selectin genes in HeLa cells upon phorbol 12-myristate 13-acetate stimulation and overcame gene repression by IkappaB alpha or IkappaB beta [16].
• Mouse embryonic fibroblasts lacking Zbtb7 are completely refractory to oncogene-mediated cellular transformation [17].
• In men, estrogens stimulate LRH release as inferred from changes in plasma bioassayable luteinizing hormone-releasing factor (LRF) activity, thus suggesting a positive feedback effect of estrogens on the hypothalamus [18].

Associations of ZBTB7A with chemical compounds

• Clomid administration (100 mg/day times 5 days) completely negates the augmented gonadotropin responses to LRF (150 mug) during late follicular and midluteal phases observed during the control studies [9].
• From this and previous data, we conclude that the increases of estradiol secretion associated with the follicular maturation and corpus luteum formation represent a major component of the feedback signal in the modulation of cyclic gonadotropin release occasioned in a large measure by the augmented pituitary sensitivity to LRF [9].
• We show that integrin stimulation up-regulated FBI-1 expression but inhibited CD79a, Requiem, c-Fos, and caspase 7 induction when the cells underwent apoptosis [19].
• Plasma FSH and LH did not respond to the administration of LRF, conjugated equine estrogens and testosterone [20].
• In addition, acute LRF responses in 14 normal men, before and at the end of 72 h of administration of 2 ml/kg/day 95% ethanol, were evaluated [21].

Physical interactions of ZBTB7A

• Finally, the conservation of crystal packing contacts suggests the probable location of the interface that mediates LRF/BCL6 complex formation [22].

Regulatory relationships of ZBTB7A

• Because LRF represses the production of the tumor suppressor p19(Arf) (ARF), it is regarded as an attractive therapeutic target for the treatment of many types of cancer [22].
• The ADH5/FDH minimal promoter is potently repressed by the FBI-1 [23].

Other interactions of ZBTB7A

• As expected from the above results, LRF and LAZ-3/BCL-6 also colocalized with each other in the nucleus [14].
• We have now identified a new member of this gene subfamily which encodes a 62 kDa Zn-finger protein, termed LRF, with a BTB/POZ domain highly similar to that of PLZF [14].

Analytical, diagnostic and therapeutic context of ZBTB7A

• Confocal microscopy showed that FBI-1 increased NF-kappaB movement into the nucleus and increased the stability of NF-kappaB in the nucleus, which enhanced NF-kappaB-mediated transcription of the E-selectin gene [16].
• No independent effect of ECS on DFS, OS, or LRF could be confirmed within the subgroup of 382 patients with LN1-3+ treated with mastectomy without radiotherapy [24].
• To ascertain whether the alpha subunit of LH is directly secreted by the pituitary or formed as a result of degradation of intact LY in the periphery, alpha subunits and intact LH were measured by radioimmunoassay in human volunteers after LRF stimulation and purified LH infusion [25].
• These events appear to be nongonadotropin-dependent in view of the absence of a pubertal pattern of pulsatile LH secretion, persistence of a prepubertal LH response to LRF even after long standing sexual precocity, prepubertal basal levels of LH and undetectable hCG, and the absence of biologically active LH-hCG by bioassay [26].
• All tumors were positive for both LRF and the alpha-subunit, whereas stainings with antisera against the beta-subunits of CG, LH, FSH, and TSH were negative [10].

References