Characterization of a novel zinc finger gene with increased expression in nondividing normal human cells.
We report here the cloning and characterization of a novel KRAB zinc finger gene, ZFQR, which has eight tandemly repeated zinc fingers, a complete KRAB box at the N-terminal region, and a unique C-terminal sequence. It is expressed in a variety of human tissues, and mRNA levels are upregulated in nondividing senescent and quiescent human fibroblasts. Overexpression of the protein in quiescent cells stimulated with serum growth factors results in inhibition of entry into the cell cycle. The latter activity is lost when the N-terminal KRAB domain is deleted. The KRAB domain is also required for the transcriptional repression activity of ZFQR and in maintaining association of the protein with the nuclear matrix. The gene has been mapped to human chromosome 19q13.4. The association of ZFQR with the nuclear matrix, transcriptional repression activity, increased expression in senescent and quiescent cells, and the ability to inhibit quiescent cells stimulated with growth factors from entering the cell cycle suggests a role for ZFQR in the maintenance of the nondividing state of normal human cells.
Ran
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Departments of Cell Biology and Medicine, Division of Molecular Virology, Roy M. and Phyllis Gough Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030-3498, USA.
Wadhwa
R
R
Bischof
O
O
Venable
S
S
Smith
J R
JR
Pereira-Smith
O M
OM
D000595:Amino Acid Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts; D017930:Genes, Reporter / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D015530:Nuclear Matrix / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D016415:Sequence Alignment; D014162:Transfection; D020798:Two-Hybrid System Techniques; D016335:Zinc Fingers / Q000235:genetics* / Q000502:physiology
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C422407:ZNF350 protein, human