Protein: Tribbles (Q9V3Z1)
Organism: Drosophila melanogaster (Fruit fly)
Function: Adapter protein that negatively regulates different signaling pathways to coordinate cell differentiation, proliferation, migration and growth. Functions by binding to key regulatory proteins and either blocks their activity or regulates their turnover by the proteasome. In various developing tissues functions as a cell cycle regulator that mediates cell proliferation according to the requirements of the developmental program. Acts by inducing the proteasomal degradation of the CD25 mitotic activators stg and twe at critical stages of development to delay entry into mitosis and thus mediate cell proliferation. During gastrulation, negatively regulates stg to delay mitosis in the ventral region of the embryonic mesoderm thus allowing invagination to be completed before cell division takes place. Delaying stg-dependent mitosis during bristle development and in migrating germline pole cells also arrests their cell divisions, whereas in cystocytes it promotes their cell divisions. Involved in the regulation of the mid-blastula transition; promotes the destruction of twe resulting in the cell cycle arrest in G2 of cycle 14 which delays mitosis and thus reduces cell proliferation allowing cell fate specification and morphogenesis to take place. In germline cells, blocks border cell migration during oogenesis by binding to slbo/C/EBP and promoting its ubiquitination and degradation by the proteasome. May function in a negative feedback loop with slbo to coordinate proper border cell migration. During tissue growth negatively regulates insulin signaling by binding to Akt1 and blocking its phosphorylation-dependent activation. However it may also function downstream in the insulin signaling pathway, acting with Akt1 to direct foxo degradation. Essential for the proper formation of operant place and aversive olfactory memories.
Subcellular location: Nucleus {ECO:0000269|PubMed:23305818, ECO:0000269|PubMed:25329475, ECO:0000269|PubMed:29025897}. Cytoplasm {ECO:0000269|PubMed:23305818, ECO:0000269|PubMed:25329475, ECO:0000269|PubMed:29025897}. Cytoplasm, cell cortex {ECO:0000269|PubMed:29025897}. Note=Weakly cytoplasmic (PubMed:29025897). In the main body follicle cells, strong nuclear accumulation at stage 10 that decreases to low levels in the cytoplasm by stage 12 (PubMed:23305818). In border cells, high levels of expression detected prior to border cell (BC) delamination (from stages 7 to 8) (PubMed:23305818). At stage 9, expression levels remains high in BC as their migration begins but decreases throughout migration. By stage 10 levels are low in BC nuclei when they arrive at the nurse cell/oocyte boundary (PubMed:23305818). {ECO:0000269|PubMed:23305818, ECO:0000269|PubMed:29025897}.
Interaction partners:
- RAC serine/threonine-protein kinase
- CCAAT/enhancer-binding protein
- M-phase inducer phosphatase
- LD22662p
- 5'-AMP-activated protein kinase subunit beta-1
Sequence:
MDNSSGQNSRTASSASTSKIVNYSSPVSPGVAAATSSSSSSSSSGMSSSQEDTVLGLFTPKKEFPNAKMLQTIREKLMTPGGACDLLALGIAAEPTDQQPVKLIQQRYLISAQPSHISAAVAAKTPASYRHLVDLTASNLRCVDIFTGEQFLCRIVNEPLHKVQRAYFQLQQHDEELRRSTIYGHPLIRPVHDIIPLTKDRTYILIAPVPQERDSTGGVTGVYENLHTYIRHAKRLCETEARAIFHQICQTVQVCHRNGIILRDLKLKRFYFIDEARTKLQYESLEGSMILDGEDDTLSDKIGCPLYTAPELLCPQQTYKGKPADMWSLGVILYTMLVGQYPFYEKANCNLITVIRHGNVQIPLTLSKSVRWLLLSLLRKDYTERMTASHIFLTPWLREQRPFHMYLPVDVEVAEDWSDAEEDEGTAADAMDDDEEGLCPLGDKHEYEDIGVEPLDYTRSTLQMAQNANGLSTEPEPDTDVDMG