The occurrence of extended acidic sequences in nonhistone chromosomal proteins

Kuehl, LeRoy; Childers, Thomas J.; McCauley, Rosalind M.

doi:10.1016/0003-9861(86)90424-8

Cited by 21 publications

(13 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Other chromatinassociated proteins, such as HMG-1 (52), also contain acidic domains. Indeed, a large class of nuclear proteins called A Ϫ proteins contain an extended region (or regions) enriched in acidic residues (19,53). This class includes various proteins whose structures are not conserved and whose functions are not identical.…”

Section: Fig 7 Western Blot Analysis Of P62 Phosphorylated In Vivomentioning

confidence: 99%

Molecular Characterization of p62, a Mitotic Apparatus Protein Required for Mitotic Progression

Ye¹,

Sloboda

1997

Journal of Biological Chemistry

View full text Add to dashboard Cite

Controlled microtubule disassembly occurs during anaphase A, the stage of mitosis characterized by the movement of the chromosomes toward the poles, an event thought to be powered by molecular motors that reside at the kinetochores. The kinetochore microtubules selectively disassemble during anaphase A, and if the microtubules are prevented from disassembling, e.g. by treatment with the microtubule stabilizing, anti-tumor drug Taxol, then mitosis ceases. Microtubule depolymerization can be induced by calcium, and calcium has been shown to result in the shortening of the distance separating the poles and movement of the chromosomes toward the poles (1). Furthermore, microtubule disassembly is necessary for the reactivation of chromosome movement in lysed cells (2), and isolated mitotic chromosomes can be translocated in association with a single microtubule in vitro as the result of microtubule depolymerization (3, 4). Thus, a critical step in anaphase is the controlled disassembly of the kinetochore microtubules.We have previously demonstrated that a protein of 62 kDa (p62), a substrate of a calcium/calmodulin-dependent protein kinase, is associated with the mitotic apparatus (5, 6). Both p62 and the kinase responsible for its phosphorylation copurify with mitotic apparatuses isolated from first cell cycle sea urchin embryos (5, 7). Importantly, the phosphorylation of p62 has been shown to correlate directly with the disassembly of microtubules in isolated mitotic apparatuses (5). Furthermore, microinjection of sea urchin embryos with affinity-purified antibodies to p62 inhibits progression through the cell cycle, specifically at the metaphase to anaphase transition (6). Because p62 is present at constant levels through at least two cell cycles (8), p62 dephosphorylation must be due to the action of a specific phosphatase and not to the degradation of the protein, as occurs, for example, with the cyclins. In fact, the existence of protein phosphatase 1 in the mitotic apparatus isolated from sea urchin embryos that dephosphorylates p62 has been demonstrated by pharmacological studies with phosphatase inhibitors (9). Finally, the subcellular localization of p62 varies with the cell cycle. During mitosis, p62 is associated with the mitotic apparatus, particularly with the microtubules (6,8,10), while during interphase, p62 resides in the nucleus (8, 10).Based on this background, our working hypothesis is that phosphorylation and dephosphorylation of p62 play key roles in controlling cell division, particularly during anaphase A, by permitting kinetochore microtubule disassembly at the appropriate time during mitosis. As the logical next step in elucidating the mode of action of p62 in mitosis, we present here a characterization of the polypeptide based on its deduced amino acid sequence obtained from cloned cDNA. The p62 polypeptide is highly acidic, yet contains distinct subdomains of alternating clusters of basic and acidic residues. Furthermore, confocal microscopy reveals that during interphase the protein bind...

show abstract

Section: Fig 7 Western Blot Analysis Of P62 Phosphorylated In Vivomentioning

confidence: 99%

Molecular Characterization of p62, a Mitotic Apparatus Protein Required for Mitotic Progression

Ye¹,

Sloboda

1997

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…In addition, a recent study looking for polyacidic regions (identified by digestion of bulk nuclear nonhistone proteins with a mixture of proteolytic enzymes and subsequent isolation of resistant peptides) suggests that such regions are significantly more common in nuclear than cytoplasmic proteins (26). Since it seems unlikely that the A-regions interact directly with DNA, what are they doing in chromatin proteins?…”

Section: A-regions In Nuclear Proteinsmentioning

confidence: 99%

Anionic regions in nuclear proteins.

Earnshaw

1987

The Journal of Cell Biology

162

View full text Add to dashboard Cite

Recent technological advances have generated a flood of protein sequence data, much of it deduced from the DNA sequences of cloned genes. In this commentary I will discuss an unexpected sequence motif found in a number of proteins that are thought to interact directly or indirectly with DNA. The motif, which I will term an A-region (acidic region), is a local high concentration of acidic residues, which may in extreme cases take the form of monotonous runs of either glutamic or aspartic acid residues. I will list below a number of proteins that have been shown to contain A-regions, and speculate about the possible role of such regions in vivo.

show abstract

“…In fact, a survey of the group of proteins containing a polyacidic cluster suggests that such a cluster is significantly more common in nuclear than cytoplasmic proteins (28). Although the precise role of the polyacidic cluster is unknown, the structure may serve as a site of electrostatic interaction with other nuclear components, for instance with histones, and thereby determines the microlocalization of proteins in the nuclear compartment.…”

mentioning

confidence: 99%

A nuclear factor containing the leucine-rich repeats expressed in murine cerebellar neurons.

Matsuoka

Taoka

Satozawa

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

A nuclear protein, termed leucine-rich acidic nuclear protein (LANP), has been Isolated from among rat cerebellar proteins whose expression was transiently increased during an early stage ofpostnatal development. The amino acid sequence, deduced from its cDNA, showed that LANP contains 247 amino acids consisting of two distinct structural doains: the N-terminal domain characterized by "leucine-rich repeat," which is found in many eukaryotic proteins and which potentially functions in mediating protein-protein interactions, and the C-terminal domain characterized by a cduster of acidic amino acids with a putative nuclear loalization signal. Immunohistochemical study using an antibody against LANP revealed that the protein is localized mainly in nuclei of Purkinje cells. In the rat cerebellum on postnatal day 7, LANP mRNA was expressed moderately in the external granule and Purklije cells and weakly in the internal granule cells. The expression in these cells, especially in Purkinje cells, increased in the second postnatal week and thereafter decreased to an adult level. The structural characteristics, localization, and the stage-and cell type-specific expression suggest a potential role of LANP in a signal transduction pathway that directs differentiation of cerebellar neurons.Morphogenesis of the mammalian central nervous system is a dynamic cellular process that includes neuronal proliferation, differentiation and migration, synaptogenesis, and synaptic rearrangement (1, 2). Several lines of evidence suggest that these morphogenetic changes result from a series of molecular events programed at a transcriptional or posttranscriptional level, such as the control of the expression of proteins during development or posttranslational modifications of expressed proteins frequently by reversible phosphorylation (3-5). Thus, one of the crucial approaches to study the morphogenetic process at the molecular level is to explore molecules that play pivotal roles in the development of the nervous system.Murine cerebellum is suitable for such an experimental analysis because (i) the cerebellum has a highly ordered geometric organization composed of a relatively small number of neuronal populations and much information has been accumulated on the development of its neuronal circuits (1, 2); (ii) mutant animals with defects of the cerebellum have become available, which enables investigation of relationships among biochemical, morphological, and physiological changes; and (iii) most of the morphogenetic changes in the murine cerebellar cortex are the early postnatal events (1, 2). On the basis of protein maps obtained by two-dimensional (2D) HPLC (6) and 2D electrophoresis (2D PAGE) we screened several hundred proteins with respect to their temporal profiles of expression during the development and identified a group of proteins whose expression transiently reached a maximum level within the first 3 postnatal weeks, the period that is most critical for murine cerebellar morphogenesis. One of those proteins, termed "V-1...

show abstract

The occurrence of extended acidic sequences in nonhistone chromosomal proteins

Cited by 21 publications

References 25 publications

Molecular Characterization of p62, a Mitotic Apparatus Protein Required for Mitotic Progression

Molecular Characterization of p62, a Mitotic Apparatus Protein Required for Mitotic Progression

Anionic regions in nuclear proteins.

A nuclear factor containing the leucine-rich repeats expressed in murine cerebellar neurons.

Contact Info

Product

Resources

About