Disease relevance of SH3GL1

• We have identified a new partner gene, EEN, fused to MLL in a case of acute myeloid leukemia [1].
• In the EEN group, hyperglycemia (serum glucose, >200 mg/dL) was observed in 4.7% of the patients vs. 9.1% in the TPN group (p = NS) [2].
• PATIENTS: Two hundred and fifty-seven patients with cancer of the stomach (n = 121), pancreas (n = 110), or esophagus (n = 26) were randomized to receive postoperative total parenteral nutrition (TPN group, n = 131) or early enteral nutrition (EEN group, n = 126) [2].
• In this prospective study including 42 patients eligible for curative gastric or colon cancer surgery; we investigated the beneficial effect of enteral immunonutrition (EEN) compared to total parenteral hyperalimentation (TPN) beginning from the preoperative period [3].

High impact information on SH3GL1

• In this study, we characterized the genomic structure of the EEN gene, including its 5' regulatory region and transcription start site (TSS) [4].
• The EEN (extra eleven nineteen) gene, located on chromosome 19p13, was cloned as a fusion with MLL from a patient with acute myeloid leukemia (AML) with translocation t(11;19)(q23;p13) [4].
• Retroviral transduction of EEN increased self-renewal and proliferation of murine hematopoietic progenitor cells [4].
• Moreover, Kasumi-1 and HL60-cell growth was inhibited with down-regulation of EEN by RNAi [4].
• Of note, overexpressed EEN showed oncogenic properties, such as transforming potential in NIH3T3 cells, stimulating cell proliferation, and increasing the activity of transcriptional factor AP-1 [4].

Biological context of SH3GL1

• Three of these transcripts are in-frame and show a peculiar tissue distribution: SH3GL2 is preferentially expressed in the brain, SH3GL3 in brain and testis, and SH3GL1 is ubiquitous [5].
• In vitro competitive binding assays demonstrate that EEN displays stronger binding affinity than Abi-1 and may compete with it for synaptojanin [6].
• EEN, an Src homology 3 (SH3) domain-containing protein in the endophilin family, has been implicated in endocytosis, although little is known about its role in leukemogenesis mediated by the MLL-EEN fusion protein [7].
• The chimeric MLL-EEN fusion protein is created as a result of chromosomal translocation t(11;19)(q23;p13) [7].
• However, EEN lacking the SH3 domain served as a dominant negative mutant that completely inhibited these effects [8].

Anatomical context of SH3GL1

• CONCLUSION: EEN represents a rational alternative to TPN in patients who undergo upper gastrointestinal tract surgery for cancer and who clinically require postoperative artificial nutrition [2].

Associations of SH3GL1 with chemical compounds

• EBP interacts simultaneously with EEN and Sos, a guanine-nucleotide exchange factor for Ras [7].
• These processes were further enhanced when EEN was present together with the wildtype but not with the non-interactive proline mutant of BPGAP1 [8].

Physical interactions of SH3GL1

• Pull-down and co-immunoprecipitation studies with deletion mutants confirmed that EEN interacted directly with BPGAP1 via its Src homology 3 (SH3) domain binding to the proline-rich region 182-PPPRPPLP-189 of BPGAP1, with prolines 184 and 186 being indispensable for this interaction [8].

Other interactions of SH3GL1

• Overexpression of EEN or BPGAP1 alone induced EGF-stimulated receptor endocytosis and ERK1/2 phosphorylation [8].
• EEN is a member of the endocytic endophilin family but its function in regulating endocytosis remains unclear [8].

Analytical, diagnostic and therapeutic context of SH3GL1

• To further explore its roles in intracellular signaling, we employed protein precipitations and matrix-assisted laser desorption/ionization mass-spectrometry and identified EEN/endophilin II as a novel partner of BPGAP1 [8].

References