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J. Biol. Chem., Vol. 280, Issue 11, 9765-9768, March 18, 2005

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Essential Role of IB Kinase in the Constitutive Processing of NF-B2 p100^*

Guoliang Qing and Gutian Xiao

From the Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854

Processing of NF-B2 precursor protein p100 to generate p52 is tightly controlled, which is important for proper function of NF-B. Accordingly, constitutive processing of p100, caused by the loss of its C-terminal processing inhibitory domain due to nfb2 gene rearrangements, is associated with the development of various lymphomas and leukemia. In contrast to the physiological processing of p100 triggered by NF-B-inducing kinase (NIK) and its downstream kinase, IB kinase (IKK), which requires the E3 ligase, -transducin repeat-containing protein (-TrCP), and occurs only in the cytoplasm, the constitutive processing of p100 is independent of -TrCP but rather is regulated by the nuclear shuttling of p100. Here, we show that constitutive processing of p100 also requires IKK, but not IKK (IB kinase ) or IKK (IB kinase ). It seems that NIK is also dispensable for this pathogenic processing of p100. These results demonstrate a general role of IKK in p100 processing under both physiological and pathogenic conditions. Additionally, we find that IKK is not required for the nuclear translocation of p100. Thus, these results also indicate that p100 nuclear translocation is not sufficient for the constitutive processing of p100.

Received for publication, October 22, 2004 , and in revised form, January 14, 2005.

^* This work was supported by Grant 704050 (to G. X.) from the New Jersey State Commission on Cancer Research and by the District #5 Ahepa/Daughters of Penelope Cancer Research Foundation, Inc. (to G. X.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Cell Biology and Neuroscience, Nelson Biological Laboratory, Rutgers, The State University of New Jersey, 604 Allison Rd., Piscataway, NJ 08854. Tel.: 732-445-2839; Fax: 732-445-5870; E-mail: xiao{at}biology.rutgers.edu.

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