Abstract
c-Jun is a transcription factor that plays an important role in regulating cell growth, apoptosis, differentiation, and transformation. The transcriptional activity of c-Jun can be regulated by both phosphorylation and sumoylation. It has also been shown that c-Jun transcription can be regulated by SuPr-1, an alternatively spliced form of SUMO-specific protease 2 (SENP2). However, the ability of SuPr-1 to enhance c-Jun transcription is dependent on promyelocytic leukemia but is independent of the desumoylation activity of SuPr-1. Here, we show that SUMO-specific protease 1 (SENP1) also markedly enhances the transcription activity of c-Jun. The action of SENP1 on c-Jun transcription is independent of the sumoylation and phosphorylation status of c-Jun but is critically dependent on the desumoylation activity of SENP1. We further show that p300 is essential for SENP1 to enhance c-Jun-dependent transcription because SENP1 can desumoylate the CRD1 domain of p300, thereby releasing the cis-repression of CRD1 on p300. Thus, two SUMO-specific proteases regulate c-Jun-dependent transcription through entirely different mechanisms.
Highlights
It is well known that c-Jun interacts with various co-regulatory proteins; this interaction can regulate the transcriptional activity of c-Jun [7, 15,16,17,18]. p300 is a well known co-activator of c-Jun [7, 16, 19, 20] that has been shown to physically interact with c-Jun and activate c-Jun-dependent transcription [16]
We further show that p300 is essential for SENP1 to enhance c-Jun-dependent transcription because SENP1 can desumoylate the CRD1 domain of p300, thereby releasing the cis-repression of CRD1 on p300
Recent studies indicate that SENP1 and SENP2 can regulate the transcriptional activity of transcription factors
Summary
It is well known that c-Jun interacts with various co-regulatory proteins; this interaction can regulate the transcriptional activity of c-Jun [7, 15,16,17,18]. p300 is a well known co-activator of c-Jun [7, 16, 19, 20] that has been shown to physically interact with c-Jun and activate c-Jun-dependent transcription [16]. We further show that p300 is essential for SENP1 to enhance c-Jun-dependent transcription because SENP1 can desumoylate the CRD1 domain of p300, thereby releasing the cis-repression of CRD1 on p300. In contrast to that of SuPr1, the desumoylation activity of SENP1 is absolutely required for its ability to induce c-Jun-dependent transcription.
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