Identification of a zinc-finger gene at 6q25: a chromosomal region implicated in development of many solid tumors

Abdollahi, Abbas; Roberts, David W.; Godwin, Andrew K.; Schultz, D.; Sonoda, Gonosuke; Testa, Joseph R.; Hamilton, Thomas C.

doi:10.1038/sj.onc.1201034

Cited by 96 publications

(80 citation statements)

References 32 publications

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“…The region between D6S1649 and D6S1637 contains the hLOT1/hZac (Abdollahi et al, 1997;Varrault et al, 1998) gene according to the Whitehead map. Although the integrity and the state of expression of this gene in our HEY cell hybrids is not clear, the proximity of our candidate region to this gene underscores the possibility that it is indeed a strong candidate tumor suppressor gene important for the control of ovarian tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Suppression of tumorigenicity in human ovarian cancer cell lines is controlled by a 2 cM fragment in chromosomal region 6q24-q25

et al. 1999

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Section: Discussionmentioning

confidence: 99%

Suppression of tumorigenicity in human ovarian cancer cell lines is controlled by a 2 cM fragment in chromosomal region 6q24-q25

et al. 1999

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“…PLAGL1 and PLAGL2 are 73 and 79% identical (83 and 90% similarity) to PLAG1, respectively, in their zinc-finger-containing region. The identity in the carboxyl-terminal regions does not exceed 30%, respectively, except for the 28 carboxyl-terminal amino acids of PLAG1 and PLAGL2, which are 79% identical (90% similarity) (Abdollahi et al, 1997b;Spengler et al, 1997;Kas et al, 1998).…”

Section: Lot1 (Zac1/plagl1) and Its Protein Structurementioning

confidence: 99%

“…The LOT1 gene contains an intron in zinc-finger 2 and additional exon/intron boundaries, which generally follow the GT-AG rule (Shapiro and Senapathy, 1987), in upstream of the coding region; whereas, the sequence between þ153 (relative to ATG site) and the last polyadenylation signal of LOT1 is devoid of introns. The presence of a putative phosphorylation site (HSPQK) for cdks is located between the second and third zinc-finger motifs (Abdollahi et al, 1997b).…”

Section: Lot1 (Zac1/plagl1) and Its Protein Structurementioning

confidence: 99%

“…In this experiment, a PCR product which was visualized in the normal (i.e., early passage) cell line but not in its malignant counterpart was isolated and used to clone the full-length rat Lot1 (rLot1) cDNA (GenBank accession number U72620) (Abdollahi et al, 1997a). Simultaneously, the human LOT1 (hLOT1) sequence was cloned (Abdollahi et al, 1997b), as is deposited in GenBank with the accession number U72621.…”

Section: The Plag Family Membersmentioning

confidence: 99%

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LOT1 (ZAC1/PLAGL1) and its family members: Mechanisms and functions

Abdollahi

2006

Journal Cellular Physiology

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Lost-on-transformation 1 (LOT1) (PLAGL1/ZAC1) is a member of the novel subfamily of zinc-finger transcription factors, designated as PLAG family. The other members in this group include PLAG1 and PLAGL2, which share high homology with each other and with LOT1, particularly in their zinc-finger amino-terminal region. They are structurally similar but functionally different. For example, the LOT1 gene encodes a growth suppressor protein and is localized on human chromosome 6q24-25, a chromosomal region that is frequently deleted in many types of human cancers. The gene is maternally imprinted and is linked to developmental disorders such as growth retardation and transient neonatal diabetes mellitus (TNDM). LOT1 is a target of growth factor signaling pathway(s) and silenced by epigenetic mechanisms, as well as by the loss of heterozygosity in different tumor tissues. PLAG1 is a protooncogene that is localized on chromosome 8q12 and was found to be a target of several types of chromosomal rearrangement including the one identified in pleomorphic adenomas of the salivary gland. Since the discovery of the PLAG family members in 1997, much has been learned about their structure and function, as are summarized in this review. While the available data suggest that these proteins may play important roles in regulating normal physiological functions in the mammals, a great deal more about their signaling pathway(s), potential role in the complex pathologies such as cancer and developmental disorders, and functional relationship between different family members and splice variants still remains to be uncovered.

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“…Zac1 inhibits tumor cell proliferation both in vitro and in vivo as a result of its induction of apoptosis and G1 cell cycle arrest (Spengler et al, 1997). Expression of Zac1 is frequently lost in tumor cell lines and down-regulated in primary tumors (Abdollahi et al, 1997b;Bilanges et al, 1999;Pagotto et al, 1999Pagotto et al, , 2000. Together, these findings suggest that Zac1 is a potential tumor suppressor gene.…”

Section: Introductionmentioning

confidence: 99%

Zinc finger protein Zac1 is expressed in chondrogenic sites of the mouse

Tsuda

Markova

Wang

et al. 2004

Developmental Dynamics

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Zac1 is a zinc finger transcription factor that elicits antiproliferative activity and is a potential tumor suppressor gene. Through a detailed spatiotemporal study by in situ hybridization of mouse embryos, we have found that Zac1 transcript is predominantly localized in developing chondrogenic tissue, in addition to the central nervous system as reported elsewhere. Zac1 is also expressed transiently in the myocardium, skeletal muscle, and basal aspect of the stratified embryonic epithelia. During cartilage development, the pattern of Zac1 expression is in close accordance with the distribution of type II collagen mRNA in mesenchymal condensation and prehypertrophic chondrocytes. In mouse ATDC5 cells undergoing in vitro chondrogenesis, the Zac1 mRNA is up-regulated in parallel with genes expressed in precartilage but the Zac1 expression is low when type II collagen mRNA is markedly increased in differentiated cells. Together, these results suggest that Zac1 is a potential regulatory gene involved in chondrogenic differentiation. Developmental Dynamics 229:340 -348, 2004.

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Identification of a zinc-finger gene at 6q25: a chromosomal region implicated in development of many solid tumors

Cited by 96 publications

References 32 publications

Suppression of tumorigenicity in human ovarian cancer cell lines is controlled by a 2 cM fragment in chromosomal region 6q24-q25

Suppression of tumorigenicity in human ovarian cancer cell lines is controlled by a 2 cM fragment in chromosomal region 6q24-q25

LOT1 (ZAC1/PLAGL1) and its family members: Mechanisms and functions

Zinc finger protein Zac1 is expressed in chondrogenic sites of the mouse

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