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Results for “Nuclear Localization Signals”

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PubMed2005

Ran GTPase regulates Mad2 localization to the nuclear pore complex.

In yeast and mammalian cells, the spindle assembly checkpoint proteins Mad1p and Mad2p localize to the nuclear pore complex (NPC) during interphase. Deletion of MAD1 or MAD2 did not affect steady-state nucleocytoplasmic distribution of a classical nuclear localization signal-containing reporter, a nuclear export signal-containing reporter, or Ran localization. We utilized cells with conditional mutations in the yeast Ran GTPase pathway to examine the relationship between Ran and targeting of checkpoint regulators to the NPC. Mutations that disrupt the concentration of Ran in the nucleus displaced Mad2p but not Mad1p from the NPC. The displacement of Mad2p in M-phase cells was correlated with activation of the spindle checkpoint. Our observations demonstrate that Mad2p localization at NPCs is sensitive to nuclear levels of Ran and suggest that release of Mad2p from NPCs is closely linked with spindle assembly checkpoint activation in yeast. This is the first evidence indicating that Ran affects the localization of Mad2p to the NPC.

Animals↗
PubMed2000

Multiple actin-related proteins of Saccharomyces cerevisiae are present in the nucleus.

An increasing number of actin-related proteins (Arps), which share the basal structure with skeletal actin but possess distinct functions, have been found in a wide variety of organisms. Individual Arps of Saccharomyces cerevisiae were classified into Arps 1-10 based on the relatedness of their sequences and functions, where Arp1 is the most similar to actin, and Arp10 is the least similar. While Arps 1-3 and their orthologs in other organisms are localized exclusively in the cytoplasm, Arp4 (also known as Act3) is localized in the nucleus and is involved in transcriptional regulation. Here we examined the more divergent Arps for possible nuclear functions. We show that Arps 5-9 are localized in the nucleus, but Arp10 is not. The nuclear export signals identified in actin are well conserved in the cytoplasmic Arps, Arps 1-3, but less conserved in the nuclear Arps. Gel filtration chromatography experiments show that the nuclear Arps are larger than monomer in size and thus are present in multi-protein complexes. Since nuclear protein complexes containing Arps are found to be responsible for histone acetylation and chromatin remodeling, it is suggested that most of the divergent Arps are involved in the !transcriptional regulation through chromatin modulation.

Actins↗
PubMed2007

RSK2 mediates muscle cell differentiation through regulation of NFAT3.

RSK2, an ERK downstream kinase, is a novel mediator of skeletal muscle cell differentiation through its regulation of NFAT3 activity. We found that the N-terminal (amino acids (aa) 1-68) and C-terminal (aa 416-674) kinase domains of RSK2 directly interacted with nuclear localization signal 1, the Ser/Pro repeat, and the polyproline domains (aa 261-365) of NFAT3. Upon A23187 stimulation, RSK2 induced nuclear localization of NFAT3. RSK2 phosphorylated NFAT3 in vitro (Km=3.559 microM), and activation of NFAT3 by RSK2 enhanced the promoter activity of NFAT3 downstream target genes in vivo. Furthermore, nuclear accumulation of NFAT3 was attenuated markedly in RSK2-/- cells compared with wild-type RSK2+/+ cells. Notably, RSK2 and NFAT3 induced a significant differentiation of C2C12 myoblasts to multinucleated myotubes. Multinucleated myotube differentiation was inhibited by small interfering RNA against RSK2, ERK1/2, or NFAT3. These results demonstrate that RSK2 is an important kinase for NFAT3 in mediating myotube differentiation.

Amino Acid Sequence↗
PubMed2000

Molecular analysis of a candidate metastasis-associated gene, MTA1: possible interaction with histone deacetylase 1.

We previously identified a novel rat candidate metastasis-associated gene, mta1, based on its differential expression in highly metastatic cells compared to nonmetastatic cells. Furthermore, we showed that overexpression of its human counterpart, MTA1, correlated with the invasiveness or lymph node metastasis of gastric, colorectal and esophageal carcinomas. The aim of this study was to analyze the domains of the MTA1 and investigate the function(s) of this protein. Structural analysis revealed that the MTA1 protein contained a GATA-like zinc-finger domain, a leucine zipper domain, a SANT domain similar to the DNA binding domain of myb-related proteins, a src homology 3-binding domain important in protein-protein interactions, two highly acidic regions characteristic of the acidic activation domains of many transcription factors, and nuclear localization signals. Immunofluorescence staining of COS-7 cells transfected with a myc-epitope-tagged MTA1 expression vector clearly showed nuclear localization of MTA1. Coimmunoprecipitation of myc-tagged MTA1 and FLAG-tagged histone deacetylase 1 (HDAC1), followed by western blot analysis using anti-myc and anti-FLAG monoclonal antibodies showed that MTA1 physically bound with HDAC1 in COS-7 cells. Together with the recent finding that the NURD (nucleosome remodeling and histone deacetylase activities) complex contains an MTA1-related gene product, named MTA2, MTA1 may be another component of this complex and be involved in the alteration of chromatin structure and transcription repression.

Animals↗
PubMed1996

Light-modulated abundance of an mRNA encoding a calmodulin-regulated, chromatin-associated NTPase in pea.

A CDNA encoding a 47 kDa nucleoside triphosphatase (NTPase) that is associated with the chromatin of pea nuclei has been cloned and sequenced. The translated sequence of the cDNA includes several domains predicted by known biochemical properties of the enzyme, including five motifs characteristic of the ATP-binding domain of many proteins, several potential casein kinase II phosphorylation sites, a helix-turn-helix region characteristic of DNA-binding proteins, and a potential calmodulin-binding domain. The deduced primary structure also includes an N-terminal sequence that is a predicted signal peptide and an internal sequence that could serve as a bipartite-type nuclear localization signal. Both in situ immunocytochemistry of pea plumules and immunoblots of purified cell fractions indicate that most of the immunodetectable NTPase is within the nucleus, a compartment proteins typically reach through nuclear pores rather than through the endoplasmic reticulum pathway. The translated sequence has some similarity to that of human lamin C, but not high enough to account for the earlier observation that IgG against human lamin C binds to the NTPase in immunoblots. Northern blot analysis shows that the NTPase MRNA is strongly expressed in etiolated plumules, but only poorly or not at all in the leaf and stem tissues of light-grown plants. Accumulation of NTPase mRNA in etiolated seedlings is stimulated by brief treatments with both red and far-red light, as is characteristic of very low-fluence phytochrome responses. Southern blotting with pea genomic DNA indicates the NTPase is likely to be encoded by a single gene.

Acid Anhydride Hydrolases↗
PubMed2006

Domains of Importin-alpha2 required for ring canal assembly during Drosophila oogenesis.

Null-mutation in Drosophila importin-alpha2, such as the deficiency imp-alpha2(D14), causes recessive female sterility with the formation of dumpless eggs. In imp-alpha2(D14) the transfer of nurse cell components to the oocyte is interrupted and the Kelch protein, an oligomeric ring canal actin organizer, is normally produced but fails to associate with the ring canals resulting in their occlusion. To define domains regulating Kelch deposition on ring canals we performed site-directed mutagenesis on protein binding domains and putative phosphorylation sites of Imp-alpha2. Phenotypic analysis of the mutant transgenes in imp-alpha2(D14) revealed that mutations affecting the Imp-beta binding-domain, the dimerization domain, and specific serine residues of putative phosphorylation sites led to a normal or nearly normal oogenesis but arrested early embryonic development, whereas mutations in the nuclear localization signal (NLS) and CAS/exportin binding domains resulted in ring canal occlusion and a drastic nuclear accumulation of the mutant proteins. Deletion of the Imp-beta binding domain also gave rise to a nuclear localization of the mutant protein, which partially retained its function in ring canal assembly. Thus, we propose that mutations in NLS and CAS binding domains affect the deposition of Kelch onto the ring canals and prevent the association of Imp-alpha2 with a negative regulator of Kelch function.

Actin Cytoskeleton↗
PubMed2003

An N-terminal segment of the active component of the bacterial genotoxin cytolethal distending toxin B (CDTB) directs CDTB into the nucleus.

Cytolethal distending toxin (CDT), produced by Actinobacillus actinomycetemcomitans, is a putative virulence factor in the pathogenesis of periodontal diseases. It is a cell cycle specific inhibitor at the G2/M transition. CDTB, one of the subunits of the CDT holotoxin, is implicated in a genotoxic role after entering the target cells, whereby chromosomal damage induces checkpoint phosphorylation cascades. CDTB microinjected into the cytoplasm was shown to localize in the nucleus and induce chromatin collapse. To investigate the molecular mechanism involved in nuclear transport of CDTB, we used transient expression and microinjection of a CDTB-green fluorescent protein (GFP) fusion protein. After microinjection, His-tagged CDTB-GFP entered the nucleus in 3-4 h. Leptomycin B did not increase the speed of entry of the fusion protein, suggesting that the relatively slow entry of the fusion protein is not due to the CRM1-dependent nuclear export of the protein. Nuclear localization of the CDTBGFP was temperature-dependent. An in vitro transport assay demonstrated that the nuclear localization of CDTB is mediated by active transport. An assay using transient expression of a series of truncated CDTB-GFP fusion proteins revealed that residues 48-124 constitute the minimum region involved in nuclear transport of CDTB. A domain swapping experiment of the region involved in nuclear transport of CDTB with an SV40 T nuclear localization signal indicated that CDTB is composed of two domains, an N-terminal domain for nuclear transport and a C-terminal active domain. Our results strongly suggest that nuclear localization of CDTB is required for the holotoxin to induce cytodistension and cell cycle block. This is the first demonstration that a bacterial toxin possessing a unique domain for nuclear transport is transferred to the animal cell nucleus by active transport.

Active Transport, Cell Nucleus↗
PubMed2005

Importin KPNA2 is required for proper nuclear localization and multiple functions of NBS1.

Nijmegen breakage syndrome (NBS) is a chromosomal-instability syndrome associated with cancer predisposition, radiosensitivity, microcephaly, and growth retardation. The NBS gene product, NBS1, is a component of the MRE11-RAD50-NBS1 (MRN) complex, a central player associated with double strand break (DSB) repair. In response to radiation, NBS1 is phosphorylated by ATM, and the MRN complex relocalizes to form punctate nuclear foci for DNA repair. NBS1 controls both the nuclear localization of the MRN complexes and radiation-induced focus formation. We report here that the KPNA2 (importin alpha1) is important for the normal nuclear localization of the MRN complex and its proper formation of the nuclear foci. KPNA2 is the only member of the importin alpha family that physically interacts with NBS1, and the KPNA2-mediated nucleus localization sequence (NLS) is mapped to amino acid residues 461-467 of NBS1 that is sufficient for both the interaction with KPNA2 and the proper nuclear localization. Inhibition of KPNA2 or blockage of the KPNA2 interaction with NBS1 results in a reduction of radiation-induced nuclear focus accumulation, DSB repair, and cell cycle checkpoint signaling of NBS1. Collectively, our results strongly suggest that an interaction with KPNA2 contributes to nuclear localization and multiple tumor suppression functions of the NBS1 complex.

Base Sequence↗
PubMed2002

Nuclear localization of peptidylarginine deiminase V and histone deimination in granulocytes.

Peptidylarginine deiminase (PAD) deiminates arginine residues in proteins to citrulline residues Ca(2+) dependently. There are four types of PADs, I, II, III, and V, in humans. We studied the subcellular distribution of PAD V in HL-60 granulocytes and peripheral blood granulocytes. Expression of green fluorescent protein-tagged PADs in HeLa cells revealed that PAD V is localized in the nucleus, whereas PAD I, II, and III are localized in the cytoplasm. PAD V deletion mutants indicated that the sequence residues 45-74 have a nuclear localization signal (NLS). A sequence feature of this NLS is a three-lysine residue cluster preceded by a proline residue and is not found in the three other PADs. Substitution of the lysine cluster by an alanine cluster abrogated the nuclear import activity. These results suggested that the NLS is a classical monopartite NLS. HL-60 granulocytes, neutrophils, and eosinophils stained with antibody specific for PAD V exhibited distinct positive signals in the nucleus. Subcellular fractionation of HL-60 granulocytes also showed the nuclear localization of the enzyme. When neutrophils were stimulated with calcium ionophore, protein deimination occurred in the nucleus. The major deiminated proteins were identified as histones H2A, H3, and H4. The implication of PAD V in histone modifications is discussed.

Alanine↗
PubMed1998

Ran-dependent signal-mediated nuclear import does not require GTP hydrolysis by Ran.

Nuclear import of classical nuclear localization sequence-containing proteins involves the assembly of an import complex at the cytoplasmic face of the nuclear pore complex (NPC) followed by movement of this complex through the NPC and release of the import substrate into the nuclear interior. This process has historically been thought to require nucleotide hydrolysis as a source of energy. We found, using hydrolysis-resistant GTP analogs and a mutant Ran unable to hydrolyze GTP, that transport of classical nuclear localization sequence containing substrate through the NPC and release of the substrate into the nucleus did not require hydrolysis of GTP by Ran. In fact, for movement of this type of import substrate into the nuclear interior we did not observe a requirement for hydrolysis of any nucleotide triphosphate. We did, however, find that a pool of free GTP (or its structural equivalent) must be added, probably because the GDP Ran that is added must be converted to GTP Ran during the import process. We found that a requirement for GTP hydrolysis can be restored to an import mixture consisting of recombinant import factors by the addition of RCC1, the Ran guanine nucleotide exchange factor.

Biological Transport↗
PubMed2026

Signaling into the nucleus through the importin 7 pathway.

Importin 7 (IPO7) is a nuclear transport receptor of the β-karyopherin family that mediates the translocation of a broad spectrum of macromolecules, commonly referred to as cargoes. Discovered nearly three decades ago, IPO7 was initially identified as an import receptor for constitutive cellular cargoes, including histone H1 and ribosomal proteins, and was shown to function synergistically and partially redundantly with canonical receptors such as importin β1 and karyopherin β2. Over the past 15 years, however, accumulating evidence has established IPO7 as an important mediator of signal-dependent nuclear trafficking in response to extracellular stimuli, including cytokines, growth factors, and cellular stress. Thus, IPO7 has emerged as a versatile nuclear transport receptor that couples extracellular signaling to dynamic changes in nuclear composition and gene expression. Mechanistically, many IPO7 cargoes lack classical nuclear localization signals and instead contain noncanonical targeting motifs that directly engage IPO7. In several cases, phosphorylation-dependent conformational changes expose these motifs, promoting IPO7 binding and translocation through the nuclear pore complex. The expanding repertoire of IPO7 cargoes, including ERK, SMAD3, EGR1, GLI1, the glucocorticoid receptor, HIF-1α, YAP1, and RUNX2, highlights its prominent role at the interface of signaling and transcriptional control. Consistent with these functions, dysregulation of IPO7-mediated transport has been implicated in cancer, hypoxia, and other pathological states. Beyond cellular signaling, IPO7 also contributes to the nuclear trafficking of viral genomes and proteins. Here, we review the molecular mechanisms of IPO7-dependent nuclear import, emerging principles of cargo recognition, and pathways that regulate IPO7 activity during cellular signaling.

NLS↗
PubMed2003

Nuclear trafficking of FGFR1: a role for the transmembrane domain.

Several members of the fibroblast growth factor (FGF) family lack signal peptide (SP) sequences and are present only in trace amounts outside the cell. However, these proteins contain nuclear localization signals (NLS) and accumulate in the cell nucleus. Our studies have shown that full length FGF receptor 1 (FGFR1) accumulates within the nuclear interior in parallel with FGF-2. We tested the hypothesis that an atypical transmembrane domain (TM) plays a role in FGFR1 trafficking into the nuclear interior. With FGFR1 destined for constitutive fusion with the plasma membrane due to its SP, how the receptor may enter the nucleus is unclear. Sequence analysis identified that FGFR1 has an atypical TM containing short stretches of hydrophobic amino acids (a.a.) interrupted by polar a.a. The beta-sheet is the predicted conformation of the FGFR1 TM, in contrast to the alpha-helical conformation of other single TM tyrosine kinase receptors, including FGFR4. Receptor trafficking in live cells was studied by confocal microscopy via C-terminal FGFR1 fusions to enhanced green fluorescent protein (EGFP) and confirmed by subcellular fractionation and Western immunoblotting. Nuclear entry of FGFR1-EGFP was independent of karyokinessis, and was observed in rapidly proliferating human TE671 cells, in slower proliferating glioma SF763 and post-mitotic bovine adrenal medullary cells (BAMC). In contrast, a chimeric FGFR1/R4-EGFP, where the TM of FGFR1 was replaced with that of FGFR4, was associated with membranes (golgi-ER, plasma, and nuclear), but was absent from the nucleus and cytosol. FGFR1delta-EGFP mutants, with hydrophobic TM a.a. replaced with polar a.a., showed reduced association with membranes and increased cytosolic/nuclear accumulation with an increase in TM hydrophilicity. FGFR1(TM-)-EGFP (TM deleted), was detected in the golgi-ER vesicles, cytosol, and nuclear interior; thus demonstrating that the FGFR1 TM does not function as a NLS. To test whether cytosolic FGFR1 provides a source of nuclear FGFR1, cells were transfected with FGFR1(SP-) (SP was deleted), resulting in cytosolic, non-membrane, protein accumulation in the cytosol and the cell nucleus. Our results indicate that an unstable association with cellular membranes is responsible for the release of FGFR1 into the cytosol and cytosolic FGFR1 constitutes the source of the nuclear receptor.

Active Transport, Cell Nucleus↗
PubMed2005

Cytoplasmic targeting of mutant poly(A)-binding protein nuclear 1 suppresses protein aggregation and toxicity in oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disorder characterized by progressive eyelid drooping, swallowing difficulties and proximal limb weakness. The autosomal dominant form of this disease is caused by a polyalanine expansion from 10 to 12-17 residues, located at the N-terminus of the poly(A)-binding protein nuclear 1 (PABPN1). A distinct pathological hallmark of OPMD is the presence of filamentous intranuclear aggregates in patients' skeletal muscle cells. Wildtype PABPN1 protein is expressed ubiquitously and was shown to be mostly concentrated in discrete nuclear domains called 'speckles'. Using an established cell- culture model, we show that most mutant PABPN1- positive (alanine expanded form) intranuclear aggregates are structures distinct from intranuclear speckles. In contrast, the promyelocytic leukaemia protein, a major component of nuclear bodies, strongly colocalized to intranuclear aggregates of mutant PABPN1. Wildtype PABPN1 can freely shuttle between the nucleus and cytoplasm. We determined whether the nuclear environment is necessary for mutant PABPN1 inclusion formation and cellular toxicity. This was achieved by inactivating the mutant PABPN1 nuclear localization signal and by generating full-length mutant PABPN1 fused to a strong nuclear export sequence. A green fluorescence protein tag inserted at the N-terminus of both wildtype PABPN1 (ala10) and mutant PABPN1 (ala17) proteins allowed us to visualize their subcellular localization. Targeting mutant PABPN1 to the cytoplasm resulted in a significant suppression of both intranuclear aggregates formation and cellular toxicity, two histological consequences of OPMD. Our results indicate that the nuclear localization of mutant PABPN1 is crucial to OPMD pathogenesis.

Amino Acid Sequence↗
PubMed1995

IFI 16 gene encodes a nuclear protein whose expression is induced by interferons in human myeloid leukaemia cell lines.

We have characterized the induction of mRNA and protein products of the human IFI 16 gene in response to IFN-gamma, IFN-alpha, and IFN-beta 2 (IL-6). We demonstrate that the IFI 16 gene product is a novel nucleoprotein expressed in association with the differentiation of myeloid precursor cell lines. In Northern blots, IFI 16 mRNA was increased approximately 25-fold above barely detectable levels in unstimulated promyelocytic HL-60 cells, in response to IFN-gamma. Other myeloid cell lines, U937 and K562, also demonstrated a marked IFN-gamma-inducibility of IFI 16 mRNA. However, all three cell lines were far less responsive to IFN-alpha, and there was no response to IL-6. By comparison, a panel of T and B cell lines demonstrated high constitutive expression of IFI 16 mRNA that was not regulated by these cytokines. Culture of HL-60 cells in medium containing dimethylsulfoxide, retinoic acid, and 1,25 dihydroxyvitamin D3, agents that stimulate the differentiation of HL-60 along myeloid pathways, also caused the induction of IFI 16 mRNA. To characterize the protein product of IFI 16, a monoclonal antibody was raised against a recombinant bacterial protein comprising the amino terminal 159 amino acids of IFI 16 fused to glutathione S-transferase. The antibody, designated 1G7, was used in Western blotting to demonstrate the strong induction of a cluster of proteins of 85-95 kDa in the nuclear extracts of IFN-gamma-treated HL-60. The nuclear localization of IFI 16 antigen was confirmed by immunohistochemical staining of HL-60 cells treated with IFN-gamma, dimethylsulfoxide, and retinoic acid. IFI 16 was also detected in the nuclei of monocytes, neutrophils, and lymphocytes in normal peripheral blood. Database comparisons of the IFI 16 amino acid sequence revealed 51% identity with the recently cloned myeloid cell nuclear differentiation antigen (MNDA), and extensive similarity to protein products of the Gene 200 cluster of IFN-inducible genes, Ifi 202 and Ifi 204. The amino terminal domain of IFI 16 encodes a putative nuclear localization signal, 124PGAQKRKK, which is strongly conserved in MNDA and 204. Nuclear IFI 16 was able to bind double-stranded DNA in vitro and exhibited a similar elution profile from DNA-cellulose as previously observed for MNDA and 204. Therefore, IFI 16 and MNDA are members of a novel family of human DNA-binding proteins whose expression is associated with myeloid cell differentiation induced by cytokines and chemical agents.

Amino Acid Sequence↗
PubMed1993

Most nuclear proteins are imported by a single pathway.

Using kinetic competition analysis, we show that the import of most Xenopus oocyte nuclear proteins is directed by a single family of nuclear localization signals (NLS). The transport of microinjected [35S]methionine-labeled nuclear proteins into oocyte nuclei was challenged with saturating concentrations of SV40 large T-antigen NLS peptide-BSA (P(Lys)-BSA) and was assessed by SDS-acrylamide gel electrophoresis and fluorography. P(Lys)-BSA was effective at competing the import of virtually all larger polypeptides but had a less marked effect on the mediated import of many smaller polypeptides. Wheat germ agglutinin, an inhibitor of nuclear pore complex function, enhanced the competitive effects of P(Lys)-BSA on the import of both large and small polypeptides. These data indicate that most 35S-labeled Xenopus oocyte nuclear proteins, including nucleoplasmin, contain NLSs that are functionally related to the T-antigen NLS and probably employ the same cytosolic NLS receptor(s).

Amino Acid Sequence↗
PubMed2005

Binding of chromium(VI) to histones: implications for chromium(VI)-induced genotoxicity.

The first evidence has been obtained for Cr(VI) (chromate) binding to isolated calf thymus (CT) histones under physiological conditions (pH 7.4, Cl(-) concentration 152 mM, 310 K). No significant Cr(VI) binding under the same conditions was observed for other extracellular and intracellular proteins, including albumin, apo-transferrin and G-actin, as well as for CT DNA. The mode of Cr(VI) binding to histones was studied by vibrational, electronic and X-ray absorption (X-ray absorption near-edge structure and X-ray absorption fine structure) spectroscopies and molecular mechanics calculations. A proposed binding mechanism includes electrostatic interactions of CrO(4) (2-) with protonated Lys and Arg residues of histones, as well as the formation of hydrogen bonds with the protein backbone. Similarly, Cr(VI) can bind to nuclear localization signals (typically, Lys- and Arg-rich fragments) of other nuclear proteins. Selective binding of Cr(VI) to newly synthesized nuclear proteins (including histones) in the cytoplasm is likely to be responsible for the active transport of Cr(VI) into the nuclei of living cells.

Animals↗
PubMed1989

Loss in transformed cells of cell cycle regulation of expression of a nuclear protein recognized by SLE patient antisera.

The identification of cellular proteins involved in the control of cell proliferation in normal cells is essential for understanding the mechanism underlying growth regulation and cellular transformation. A nuclear protein termed Ki antigen with a relative mobility of 32,000 (Mr 32K) and which is recognized by SLE patient antisera has been identified in cells of human, bovine, and murine origin. Recently, cDNA clones for the bovine and human Ki antigens have been isolated using SLE patient antisera (T. Nikaido, et al., in preparation). The nucleotide sequence predicted a protein of 239 amino acids with a possible nuclear localization signal resembling that identified in SV40 T antigen and other nuclear proteins. Here we show that the expression of Ki antigen is regulated in the normal cell, but not in the transformed cell. Furthermore, in the K-ras temperature-sensitive mutant cell line, ts 371 normal rat kidney (NRK), Ki antigen expression increases several-fold at the permissive temperature relative to the nonpermissive temperature. These results suggest that expression of Ki antigen might be correlated with cellular transformation as well as with cell growth regulation.

Animals↗