Proteasome degradation

F-adjacent Transcript-10 (FAT 10) is composed of two ubiquitin-like domains and capable to mark conjugated proteins for proteasomal degradation independent of ubiquitin. FAT10 is inducible by IFN-y and TNF and induces apoptosis when over expressed. 

Ubiquitin/Proteasome. Figure 2 Functional consequences of ubiquitin linkage. Substrates (blue bars) are linked via lysine residues (K) to ubiquitin or ubiquitin chains, (a) Attachment of chains connected via Lysines in position 48 of ubiquitin (K48) targets substrates for proteasomal degradation. In contrast modification of one (b) or multiple (c) lysines by a single ubiquitin molecule mediates novel protein interactions or initiates endocytosis. Conjugation of K63-linked polyubiquitin (d) alters protein function and can also serve as a signal for endocytosis. 

Proteasomal degradation also plays an essential role in the activation of cellular signaling pathways. A prototype for this is the control of NF-kB signaling, which has a pivotal role in inflammatory responses. Upon stimulation the inhibitory IicBa protein is phos-phorylated and thereby becomes a target substrate for K48-polyubiquitination. Proteasomal degradation of IkBu releases the transcription factor NF-kB, which subsequently translocates to the nucleus and activates specific target genes. 

As proposed schematically in Fig. 13.2, RNI may block PHD-activity, attenuate proline hydroxylation of HIF-la, dissociate HIF-la from pVHL with the consequence of protein stabilization based on decreased proteasomal degradation. 

Parkin substrates. (B) A model for Parkin-dependent degradation of misfolded proteins. Parkin recruits a complex containing molecular chaperones and the unfolded substrates to the proteasome. Degradation may be facilitated by... 

Zhang, J. G., et al.. The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation. Proc Nad Acad Sci USA, 1999, 96(5), 2071-6. 

Meacham, G. C., et al.. The Hsc70 cochaperone CHIP targets immature CFTR for proteasomal degradation. Nat Cell Biol, 2001, 3(1), 100-5. 

Magnieico, a., et al., WW domain HFCT F3s target Cbl RING finger F3s for proteasomal degradation. J Biol Chem, 2003, 278(44), 43169-77. 

UBC4 148 [24] Unknown DoalO Rsp5 Proteasomal degradation of diverse shortlived proteins [24] Proteasomal degradation of MATa2 transcriptional repressor [49] Endocytosis of membrane proteins [60, 61] protein trafficking (see Ref [63])... 

UBC7 165 [25] Hrdl [39] DoalO [42] Localized to ER membrane via Cuel [37] Role in proteasomal degradation via ERAD [38, 48] confers resistance to cadmium and other ER stresses [25] In conjunction with Ubc7, proteasomal turnover of MATa2... 

UBC8 206 [160] Unknown Glucose-induced proteasome degradation of fructose-1,6-bisphosphatase [57]... 

Ubc7 is localized to the endoplasmic reticulum (ER) through an interaction with a partner protein, Cuel [37], and plays a major role in proteasome degradation. 

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