Disease relevance of SBF1

• It is striking to note that mutations in MTMR13 also cause peripheral neuropathy with myelin outfoldings, although it belongs to a pseudophosphatase subgroup, since its closest homologue is MTMR5/Sbf1 [1].
• Mice that are nullizygous for Sbf1 exhibit male infertility characterized by azoospermia [2].

High impact information on SBF1

• In contrast with myotubularin, Sbf1 lacks a functional catalytic domain which dephosphorylates phospho-tyrosine and serine-containing peptides in vitro [3].
• Competitive interference of endogenous SET domain-dsPTPase interactions by forced expression of Sbf1 induced oncogenic transformation of NIH 3T3 fibroblasts and impaired the in vitro differentiation of C2 myoblast cells [3].
• The nullizygous phenotype in conjunction with high-level expression of Sbf1 in premeiotic germ cells and Sertoli's cells is consistent with a crucial role for Sbf1 in transition from diploid to haploid spermatocytes [2].
• Male infertility, impaired spermatogenesis, and azoospermia in mice deficient for the pseudophosphatase Sbf1 [2].
• We demonstrate here that Sbf1, a pseudophosphatase of the myotubularin family, is expressed at high levels in seminiferous tubules of the testis, specifically in Sertoli's cells, spermatogonia, and pachytene spermatocytes, but not in postmeiotic round spermatids [2].

Biological context of SBF1

• Since SBF1 governs the formation kinetics and composition of the initial precursor spheres, we hypothesized that the pH of the SBF1 solution will also influence the final structure of the SBF2-derived crystalline apatite [4].
• Silencer region of a chalcone synthase promoter contains multiple binding sites for a factor, SBF-1, closely related to GT-1 [5].

Anatomical context of SBF1

• Conversely, deletion of its conserved N-terminal 44 amino acids alone was sufficient to convert Sbf1 from an inhibitor of cellular growth to a transforming protein in NIH 3T3 cells [6].
• Oncogenic forms of Sbf1 partially localized to the nucleus, in contrast to the exclusively cytoplasmic subcellular localization of endogenous Sbf1 in all cell lines and mammalian tissues tested [6].

Associations of SBF1 with chemical compounds

• To test this hypothesis, polystyrene substrates were immersed into SBF1 with different pH (5.8 or 6.5), and then immersed into the identical SBF2 (pH=6.0) [4].
• In SBF-1, the deposits were mainly of brushite type [7].

Enzymatic interactions of SBF1

• Growth suppression as well as the ability of SUV39H1 to form nuclear bodies and silence transcription are antagonized by the oncogenic antiphosphatase Sbf1 that when hyperexpressed interacts with the SET domain and stabilizes the phosphorylated form of SUV39H1 [8].

Other interactions of SBF1

• Through this interaction, MTMR5 increases the enzymatic activity of MTMR2 and dictates its subcellular localization [9].
• Regulation of myotubularin-related (MTMR)2 phosphatidylinositol phosphatase by MTMR5, a catalytically inactive phosphatase [9].
• Sbf1 (SET binding factor 1) is a pseudo-phosphatase related to the myotubularin family of dual specificity phosphatases, some of which have been implicated in cellular growth and differentiation by virtue of their mutation in human genetic disorders [6].
• The interacting protein was shown by mass spectrometry to be MTMR5, a catalytically inactive member of the MTM family [9].

Analytical, diagnostic and therapeutic context of SBF1

• Bean nuclear extracts were used in gel retardation assays and DNase I footprinting experiments to identify a protein factor, designated SBF-1, that specifically interacts with regulatory sequences in the promoter of the bean defense gene CHS15, which encodes the flavonoid biosynthetic enzyme chalcone synthase [5].

References