E3 ubiquitin-protein ligase TRIM33

Definition:

Acts as an E3 ubiquitin-protein ligase. Promotes SMAD4 ubiquitination, nuclear exclusion and degradation via the ubiquitin proteasome pathway. According to PubMed:16751102, does not promote a decrease in the level of endogenous SMAD4. May act as a transcriptional repressor. Inhibits the transcriptional response to TGF-beta/BMP signaling cascade. Plays a role in the control of cell proliferation. Its association with SMAD2 and SMAD3 stimulates erythroid differentiation of hematopoietic stem/progenitor (By similarity). Monoubiquitinates SMAD4 and acts as an inhibitor of SMAD4-dependent TGF-beta/BMP signaling cascade (Monoubiquitination of SMAD4 hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade).

References:

[1]. L Venturini, et al. TIF1gamma, a novel member of the transcriptional intermediary factor 1 family. Oncogene. 1999 Feb 4;18(5):1209-17. [Content Brief]

[2]. Wei He, et al. Hematopoiesis controlled by distinct TIF1gamma and Smad4 branches of the TGFbeta pathway. Cell. 2006 Jun 2;125(5):929-41. [Content Brief]

[3]. Sirio Dupont, et al. Germ-layer specification and control of cell growth by Ectodermin, a Smad4 ubiquitin ligase. Cell. 2005 Apr 8;121(1):87-99. [Content Brief]

[4]. Sirio Dupont, et al. FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination. Cell. 2009 Jan 9;136(1):123-35. [Content Brief]

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