(minichromosome shown to interact with MAPK6 (extracellular

(minichromosome
maintenance protein 7) and hScrib (human analog of Drosophila Scribble tumor
suppressor protein) (Scheffner,
Huibregtse et al. 1993; Liu, Yuan et al. 2005; Liu, Disbrow et al. 2007). Later studies showed that Ube3a
could act as a ubiquitin ligase independent of E6 protein and target proteins
such as HHR23A (human homolog of the yeast DNA repair protein RAD23) (Kumar,
Talis et al. 1999), Mcm-7 (Kuhne
and Banks 1998), p53 (Mishra
and Jana 2008), tumor suppressor TSC2 (Zheng,
Ding et al. 2008) and hypoxia-inducible factor 1?
regulator HIF1AN (Martinez-Noel,
Galligan et al.) for degradation. These studies
suggested the importance of Ube3a in regulating DNA repair and cell cycle
progression. Subsequently it was shown that Ube3a could target itself for
degradation in vitro (Nuber,
Schwarz et al. 1998). This was corroborated by the
finding in vivo that overexpressed Ube3a promoted its own poly- ubiquitination
and degradation via the proteasome system (Kao,
Beaudenon et al. 2000). This process
of inactivating and degrading unbound Ube3a molecules may be a regulatory
mechanism for controlling intracellular Ube3a levels. Ube3a has also been shown
to interact with MAPK6 (extracellular signal-regulated kinase 3 or ERK3) (Martinez-Noel,
Galligan et al.), which has been shown to play an
importantrole in neural morphogenesis through regulation of neuronal
cytoskeleton and dendrite spine formation (Brand,
Schumacher et al.).

Transcription
and UPS are completely disparate pathways. Transcription is the beginning of
the life of a protein whereas proteolysis is the end. However, it has been
shown that the components of the ubiquitin proteasome system are also involved
in transcriptional regulation. Ube3a has been shown to play an important role
in the regulation of activity of many nuclear receptors. UBE3A levels are
reduced in human invasive breast and prostate cancers compared to the adjacent
normal tissues. The reduction in UBE3A is accompanied with concomitant increase
in the levels of estrogen 

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