High impact information on ULK1

• Previous studies showed that the serine/threonine kinase Unc51.1 is one of the earliest genes in neuronal differentiation and is required for granule cell axon formation [1].
• Transient expression of the six ATG-1-translated 4.1R isoforms tagged with a c-Myc epitope revealed that all of them predominantly distributed to the plasma membrane and the endoplasmic reticulum [2].
• In contrast to findings in yeast, induction of autophagy by Atg1 is dependent on its kinase activity [3].
• CONCLUSIONS: Our results reveal a central role for Atg1 in mounting a coordinated autophagic response and demonstrate that autophagy has the capacity to induce cell death [3].
• Direct induction of autophagy by atg1 inhibits cell growth and induces apoptotic cell death [3].

Biological context of ULK1

• Both FISH and RH mapping confirmed the regional localization of ULK1 to human chromosome 12q24.3 [4].
• Sequence analysis of the human ULK1 cDNA showed that an open reading frame is composed of 1050 amino acids with a calculated MW of 112.6 kDa and a pI of 8.80 [4].
• Southern blot analyses suggested that the ULK1 gene spans 30-40 kb in the human genome as a single-copy gene [4].
• Amino acid starvation or rapamycin treatment, which upregulates autophagy, causes a redistribution of mAtg9 from the TGN to peripheral, endosomal membranes, which are positive for the autophagosomal marker GFP-LC3. siRNA-mediated depletion of the putative mammalian homologue of Atg1p, ULK1, inhibits this starvation-induced redistribution [5].
• Theses findings indicated that ULK2 is involved in apoptosis through p53 pathway [6].

Anatomical context of ULK1

• In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized [7].
• Northern blot analysis revealed that ULK1 is ubiquitously expressed in adult human tissues such as skeletal muscle, heart, pancreas, brain, placenta, liver, kidney, and lung, whereas UNC-51 is specifically detected in the nervous system of C. elegans [4].
• We identified two mammalian ULK1 (Unc-51-like kinase involved in neurite extension) binding proteins by yeast two-hybrid screening [7].
• Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes [5].
• In control experiments, the patterns of the biologic effects of preimmune rIgG or hIgG preparations were similar to those of rATG and hATG, indicating a nonspecific nature of the effects of ATG on progenitor cells [8].

Associations of ULK1 with chemical compounds

• Phylogenetic analysis of ULK1, UNC-51, and Apglp suggested that they constitute a novel subfamily of serine/threonine kinases [4].
• Human ULK1, a novel serine/threonine kinase related to UNC-51 kinase of Caenorhabditis elegans: cDNA cloning, expression, and chromosomal assignment [4].

Other interactions of ULK1

• Mouse ULK2 cDNA encodes a putative polypeptide of 1033 aa which has an overall 52% and 33% amino acid identity to ULK1 and UNC-51, respectively [9].

Analytical, diagnostic and therapeutic context of ULK1

• Here we report the molecular cloning and characterization of the human homologue of UNC-51, designated ULK1, for UNC-51 (C. elegans)-like kinase 1 [4].

References