Disease relevance of SEPT1

• AF17q25, a putative septin family gene, fuses the MLL gene in acute myeloid leukemia with t(11;17)(q23;q25) [1].
• Analysis of mammalian septin expression in human malignant brain tumors [2].
• Sint1, a common integration site in SL3-3-induced T-cell lymphomas, harbors a putative proto-oncogene with homology to the septin gene family [3].
• FLJ10849, a septin family gene, fuses MLL in a novel leukemia cell line CNLBC1 derived from chronic neutrophilic leukemia in transformation with t(4;11)(q21;q23) [4].
• The established cell line, CNLBC1, could provide a useful model for analyzing the pathogenesis of MLL-septin leukemias and chronic neutrophilic leukemia [4].

High impact information on SEPT1

• The septin CDCrel-1 binds syntaxin and inhibits exocytosis [5].
• Similarly, the ability of plasma to enable activation of neutrophils by LPS (LBP/Septin activity) was depleted and recovered by the same process [6].
• Septin: a factor in plasma that opsonizes lipopolysaccharide-bearing particles for recognition by CD14 on phagocytes [7].
• A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif [8].
• Unlike related septin gene products, ARTS is localized to mitochondria and translocates to the nucleus when apoptosis occurs [8].

Biological context of SEPT1

• We analyzed one patient with de novo AML and one with therapy-related AML with t(11;17)(q23;q25) and identified the AF17q25 gene on chromosome 17q25, a putative septin family gene, fused with MLL [1].
• Using RNA interference, we found that suppression of septin expression in HeLa cells caused a pronounced increase in microtubule stability [9].
• Moreover, septin depletion increased the number of cells with abnormal nuclei, and this effect was blocked by gene silencing of MAP4 [9].
• Fluorescence in situ hybridization demonstrated a rearrangement of the MLL gene and molecular genetic analyses identified a septin family gene, SEPT2, located on chromosome 2q37, as the fusion partner of MLL [10].
• The present paper reports a comprehensive study of septin gene expression by DNA microarray methods in 10 360 samples of normal, diseased, and tumour tissues [11].

Anatomical context of SEPT1

• Unlike lower eukaryotic cells, the physiological significance of mammalian septin complexes is largely unknown [12].
• One of these clones, DIFF6, is derived from an RNA whose expression level is higher in several cell lines producing high amounts of MEL-14-reactive gp90, and absent or present at lower levels in several cell lines expressing low levels of this glycoprotein [13].
• Overproduction of Mid2p depolarizes cell growth and affects the organization of both the septin and actin cytoskeletons [14].
• This model cannot, however, explain the GTP-biochemistry of heteromeric septin complexes from cytosol [15].
• These results strongly suggest that septin filaments may interact not only with actin filaments but also with microtubule networks and that GTPase activity of MSF-A is not indispensable to incorporation of MSF-A into septin filaments [16].

Associations of SEPT1 with chemical compounds

• Parkin functions as a ubiquitin protein ligase in the degradation of several proteins, including the neuron-specific septin CDCrel-1 [17].
• Moreover, Rab35 is involved in the intercellular bridge localization of two molecules essential for the postfurrowing steps of cytokinesis: the phosphatidylinositol 4,5-bis phosphate (PIP2) lipid and the septin SEPT2 [18].
• Studies have shown that septin 1 with site-directed mutations of five serine residues (Ser19, Ser206, Ser307, Ser312 and Ser315) has a much lower degree of aggregation and better structural homogeneity and that the mutations cause only slight perturbations in the secondary structure of septin 1 [19].

Regulatory relationships of SEPT1

• In intact cells, MAP4 was required for the stabilization of microtubules induced by septin depletion [9].
• These results suggest that Mid2p influences septin ring organization at the site of cell division and its turnover might normally be required to permit septin ring disassembly [14].
• We propose that the Rab35-regulated pathway plays an essential role during the terminal steps of cytokinesis by controlling septin and PIP2 subcellular distribution during cell division [18].

Other interactions of SEPT1

• It is shown that SEPT13 and the other known human septins are expressed in all tissue types but some show high expression in lymphoid (SEPT1, 6, 9, and 12) or brain tissues (SEPT2, 3, 4, 5, 7, 8, and 11) [11].
• These results suggest that AF17q25 and hCDCrel might define a new septin family particularly involved in the pathogenesis of 11q23-associated leukemia [1].
• A novel septin, SEPT13, has been identified and is shown to be related to SEPT7 [11].
• Mass spectroscopic analysis of proteins coprecipitating with Sept6 identified the microtubule-associated protein MAP4 as a septin binding partner [9].
• The novel human platelet septin SEPT8 is an interaction partner of SEPT4 [20].

Analytical, diagnostic and therapeutic context of SEPT1

• An anillin homologue, Mid2p, acts during fission yeast cytokinesis to organize the septin ring and promote cell separation [14].
• SA-RhoGEF was found by immunoprecipitation analysis to associate with septin complexes in REF52 fibroblast cells, maybe through direct interaction with Sept9b [21].
• Investigation of the identified Ov/Br septin isoforms by RT-PCR confirms a complex transcriptional pattern, with several isoforms showing tissue-specific distribution [22].
• Quantitative PCR confirmed the upregulation of the putative septin by neuronal differentiation and northern blotting showed only one band corresponding to sep3B with a neurospecific expression pattern in adult human tissues [23].
• Crystallization and preliminary crystallographic studies of human septin 1 with site-directed mutations [19].

References