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Q Q Cai

Publications and source records attributed to Q Q Cai.

6 recordsLinked to original sources

The serum response factor nuclear localization signal: general implications for cyclic AMP-dependent protein kinase activity in control of nuclear translocation.

We have identified a basic sequence in the N-terminal region of the 67-kDa serum response factor (p67SRF or SRF) responsible for its nuclear localization. A peptide containing this nuclear localization signal (NLS) translocates rabbit immunoglobulin G (IgG) into the nucleus as efficiently as a peptide encoding the simian virus 40 NLS. This effect is abolished by substituting any two of the four basic residues in this NLS. Overexpression of a modified form of SRF in which these basic residues have been mutated confirms the absolute requirement for this sequence, and not the other basic amino acid sequences adjacent to it, in the nuclear localization of SRF. Since this NLS is in close proximity to potential phosphorylation sites for the cAMP-dependent protein kinase (A-kinase), we further investigated if A-kinase plays a role in the nuclear location of SRF. The nuclear transport of SRF proteins requires basal A-kinase activity, since inhibition of A-kinase by using either the specific inhibitory peptide PKIm or type II regulatory subunits (RII) completely prevents the nuclear localization of plasmid-expressed tagged SRF or an SRF-NLS-IgG conjugate. Direct phosphorylation of SRF by A-kinase can be discounted in this effect, since mutation of the putative phosphorylation sites in either the NLS peptide or the encoded full-length SRF protein had no effect on nuclear transport of the mutants. Finally, in support of an implication of A-kinase-dependent phosphorylation in a more general mechanism affecting nuclear import, we show that the nuclear transport of a simian virus 40-NLS-conjugated IgG or purified cyclin A protein is also blocked by inhibition of A-kinase, even though neither contains any potential sites for phosphorylation by A-kinase or can be phosphorylated by A-kinase in vitro.

Amino Acid Sequence↗

17 beta Hydroxysteroid dehydrogenase 1 "pseudogene" is differentially transcribed: still a candidate for the breast-ovarian cancer susceptibility gene (BRCA1).

BRCA1, the susceptibility gene for hereditary breast-ovarian cancer, is located on chromosome 17q12-21 but has not yet been identified. Two tandem oestradiol 17 beta hydroxysteroid dehydrogenase genes (17HSD) are assigned to this region. The active 17HSDII gene encodes the normal enzyme which regulates local synthesis of oestrogens, whereas 17HSDI is considered to be a pseudogene. We used reverse transcription coupled to polymerase chain reaction (RT-PCR) and found that the 17HSDI gene was also transcribed in half of the human cell lines and most of the biopsies studied, suggesting that 17HSDI could modulate normal 17HSDII activity in oestrogen target cells. We hypothesize that altered 17HSDI gene expression could lead to both hereditary and/or sporadic breast cancer by increasing local oestrogen concentration and that it is still a potential candidate for BRCA1.

17-Hydroxysteroid Dehydrogenases↗

Chromosomal location and expression of the genes coding for Ku p70 and p80 in human cell lines and normal tissues.

Ku protein is a relatively abundant DNA-binding nuclear protein complex composed of two polypeptide subunits, p70 and p80. Ku has been recently identified as the regulatory component of the DNA-dependent protein kinase that phosphorylates RNA polymerase II. To further characterize in vivo regulation of Ku protein, we studied the expression of the transcripts coding for the Ku p70 and p80 subunits in different human cell lines and normal tissues by Northern blot hybridization, using specific cDNA probes. The expression level of both genes was approximately 10-fold higher in established cell lines than in normal tissues. However, mRNA expression levels in permanent cell lines correlated more strongly with their proliferative state than with their level of malignant transformation. In purified T lymphocytes induced to proliferate by the combined action of monoclonal antibodies directed against the CD2 and CD28 adhesion molecules, Ku p70 and p80 mRNA steady-state levels increased as soon as 6 h after activation and lasted at least 72 h. The human genes coding for the Ku p70 and p80 subunits were localized by cytogenetic mapping, using fluorescence in situ hybridization, to 22q13 and 2q33-->q35, respectively.

Antigens, Nuclear↗