Disease relevance of STAMBP

• The potential functions of RNF11-mediated degradation of AMSH in breast cancer are discussed [1].
• We also show that a catalytically inactive AMSH inhibits retroviral budding in a dominant-negative manner and induces the accumulation of ubiquitinated forms of an endosomal cargo, namely murine leukemia virus Gag [2].

High impact information on STAMBP

• Two deubiquitinating enzymes, AMSH and UBPY, interact with ESCRT protein components but exert opposite effects upon the rate of epidermal growth factor receptor downregulation [3].
• An inactivating mutation (D348A) in AMSH leads to accumulation of ubiquitin on endosomes and the concomitant stabilization of a ubiquitinated form of STAM, which requires an intact ubiquitin interaction motif (UIM) within STAM [4].
• We propose that AMSH is a deubiquitinating enzyme with functions at the endosome, which oppose the ubiquitin-dependent sorting of receptors to lysosomes [4].
• Loss of neurons in the hippocampus and cerebral cortex of AMSH-deficient mice [5].
• Furthermore, AMSH-deficient hippocampal neuronal cells were unable to survive in vitro, even in the presence of several stimulatory cytokines, while AMSH-deficient cerebellar neurons, thymocytes, and embryonic fibroblasts survived normally [5].

Biological context of STAMBP

• The AMSH-deficient mice were morphologically indistinguishable from their littermates at birth, and histopathological examinations revealed normal morphogenesis in all tissues tested [5].
• We molecularly cloned a novel molecule interacting with the SH3 domain of STAM, which was named AMSH (associated molecule with the SH3 domain of STAM) [6].
• Possible involvement of a novel STAM-associated molecule "AMSH" in intracellular signal transduction mediated by cytokines [6].
• The deubiquitinase AMSH (associated molecule with the SH3 domain of signal transducing adaptor molecule) specifically interacts with phosphorylated Xp95 in M-phase cell lysates [7].

Anatomical context of STAMBP

• AMSH mutant deleted of the C-terminal half conferred dominant negative effects on signaling for DNA synthesis and c-myc induction mediated by interleukin 2 and granulocyte macrophage-colony-stimulating factor [6].

Associations of STAMBP with chemical compounds

• However, all the AMSH-deficient mice exhibited postnatal growth retardation and died between postnatal day 19 (P19) and P23 [5].
• Targeting of AMSH to Endosomes Is Required for Epidermal Growth Factor Receptor Degradation [8].

Physical interactions of STAMBP

• Here, we show that RNF11 binds to AMSH in mammalian cells and that this interaction is independent of the RNF11 RING-finger domain and the PY motif [1].
• In contrast, a mutant of AMSH that lacks the ability to bind STAM localized normally on endosomes [9].

Regulatory relationships of STAMBP

• CONCLUSIONS: This report implicates AMSH and AMSH-2 as a novel family of molecules that positively regulate the TGF-beta signaling pathway [10].

Other interactions of STAMBP

• We have looked for similar activity in associated molecule with the SH3 domain of STAM (AMSH), a JAMM domain-containing protein that associates with the SH3-domain of STAM, a protein, which regulates receptor sorting at the endosome [4].
• These results suggest that AMSH-LP and AMSH may have different functions [11].
• These results suggest that AMSH plays a critical role in the cytokine-mediated intracellular signal transduction downstream of the Jak2/Jak3.STAM complex [6].
• However, deletion of the clathrin-binding site from the proteins, as well as RNA interference-mediated depletion of clathrin heavy chain, resulted in a failure of AMSH and AMSH-LP to localize on endosomes [9].
• In particular, we show that two further MIT domain-containing proteins (AMSH/STAMBP and LOC129531) interact with multiple components of the human ESCRT III complex [12].

Analytical, diagnostic and therapeutic context of STAMBP

• To investigate the in vivo functional role of AMSH, we have generated AMSH-deficient mice by gene targeting [5].

References